Molecular cell biology sixth editionPDF电子书下载
- 电子书积分:30 积分如何计算积分?
- 作 者:harvey ldish and arnold berk and chris a.kaiser and monty krieger and matthew p.scott
- 出 版 社:w.h.freeman and company
- 出版年份:2008
- ISBN:1429203142
- 页数:1229 页
Part Ⅰ Chemical and Molecular Foundations 1
1 LIFE BEGINS WITH CELLS 1
1.1 The Diversity and Commonality of Cells 1
All Cells Are Prokaryotic or Eukaryotic 1
Unicellular Organisms Help and Hurt Us 4
Viruses Are the Ultimate Parasites 6
Changes in Cells Underlie Evolution 6
Even Single Cells Can Have Sex 7
We Develop from a Single Cell 8
Stem Cells,Fundamental to Forming Tissues and Organs,Offer Medical Opportunities 8
1.2 The Molecules of a Cell 9
Small Molecules Carry Energy,Transmit Signals,and Are Linked into Macromolecules 9
Proteins Give Cells Structure and Perform Most Cellular Tasks 10
Nucleic Acids Carry Coded Information for Making Proteins at the Right Time and Place 11
The Genome Is Packaged into Chromosomes and Replicated During Cell Division 12
Mutations May Be Good,Bad,or Indifferent 13
1.3 The Work of Cells 14
Cells Build and Degrade Numerous Molecules and Structures 15
Animal Cells Produce Their Own External Environment and Glues 16
Cells Change Shape and Move 16
Cells Sense and Send Information 16
Cells Regulate Their Gene Expression to Meet Changing Needs 17
Cells Grow and Divide 18
Cells Die from Aggravated Assault or an Internal Program 19
1.4 Investigating Cells and Their Parts 20
Cell Biology Reveals the Size,Shape,Location,and Movements of Cell Components 20
Biochemistry and Biophysics Reveal the Molecular Structure and Chemistry of Purified Cell Constituents 21
Genetics Reveals the Consequences of Damaged Genes 22
Genomics Reveals Differences in the Structure and Expression of Entire Genomes 23
Developmental Biology Reveals Changes in the Properties of Cells as They Specialize 23
Choosing the Right Experimental Organism for the Job 25
The Most Successful Biological Studies Use Multiple Approaches 27
1.5 A Genome Perspective on Evolution 28
Metabolic Proteins,the Genetic Code,and Organelle Structures Are Nearly Universal 28
Darwin’s Ideas About the Evolution of Whole Animals Are Relevant to Genes 28
Many Genes Controlling Development Are Remarkably Similar in Humans and Other Animals 28
Human Medicine Is Informed by Research on Other Organisms 29
2 CHEMICAL FOUNDATIONS 31
2.1 Covalent Bonds and Noncovalent Interactions 32
The Electronic Structure of an Atom Determines the Number and Geometry of Covalent Bonds It Can Make 33
Electrons May Be Shared Equally or Unequally in Covalent Bonds 34
Covalent Bonds Are Much Stronger and More Stable Than Noncovalent Interactions 35
Ionic Interactions Are Attractions between Oppositely Charged Ions 36
Hydrogen Bonds Determine the Water Solubility of Uncharged Molecules 37
Van der Waals Interactions Are Caused by Transient Dipoles 37
The Hydrophobic Effect Causes Nonpolar Molecules to Adhere to One Another 38
Molecular Complementarity Mediated via Noncovalent Interactions Permits Tight,Highly Specific Binding of Biomolecules 39
2.2 Chemical Building Blocks of Cells 40
Amino Acids Differing Only in Their Side Chains Compose Proteins 41
Five Different Nucleotides Are Used to Build Nucleic Acids 44
Monosaccharides Joined by Glycosidic Bonds Form Linear and Branched Polysaccharides 44
Phospholipids Associate Noncovalently to Form the Basic Bilayer Structure of Biomembranes 46
2.3 Chemical Equilibrium 49
Equilibrium Constants Reflect the Extent of a Chemical Reaction 50
Chemical Reactions in Cells Are at Steady State 50
Dissociation Constants of Binding Reactions Reflect the Affinity of Interacting Molecules 50
Biological Fluids Have Characteristic pH Values 51
Hydrogen Ions Are Released by Acids and Taken Up by Bases 52
Buffers Maintain the pH of Intracellular and Extracellular Fluids 52
2.4 Biochemical Energetics 54
Several Forms of Energy Are Important in Biological Systems 54
Cells Can Transform One Type of Energy into Another 55
The Change in Free Energy Determines the Direction of a Chemical Reaction 55
The △G°’ of a Reaction Can Be Calculated from Its Keq 56
The Rate of a Reaction Depends on the Activation Energy Necessary to Energize the Reactants into a Transition State 56
Life Depends on the Coupling of Unfavorable Chemical Reactions with Energetically Favorable Reactions 57
Hydrolysis of ATP Releases Substantial Free Energy and Drives Many Cellular Processes 57
ATP Is Generated During Photosynthesis and Respiration 59
NAD+ and FAD Couple Many Biological Oxidation and Reduction Reactions 59
3 PROTEIN STRUCTURE AND FUNCTION 63
3.1 Hierarchical Structure of Proteins 64
The Primary Structure of a Protein Is Its Linear Arrangement of Amino Acids 65
Secondary Structures Are the Core Elements of Protein Architecture 66
Overall Folding of a Polypeptide Chain Yields Its Tertiary Structure 67
Different Ways of Depicting the Conformation of Proteins Convey Different Types of Information 68
Structural Motifs Are Regular Combinations of Secondary and Tertiary Structures 68
Structural and Functional Domains Are Modules of Tertiary Structure 70
Proteins Associate into Multimeric Structures and Macromolecular Assemblies 72
Members of Protein Families Have a Common Evolutionary Ancestor 72
3.2 Protein Folding 74
Planar Peptide Bonds Limit the Shapes into Which Proteins Can Fold 74
Information Directing a Protein’s Folding Is Encoded in Its Amino Acid Sequence 74
Folding of Proteins in Vivo Is Promoted by Chaperones 75
Alternatively Folded Proteins Are Implicated in Diseases 77
3.3 Protein Function 78
Specific Binding of Ligands Underlies the Functions of Most Proteins 78
Enzymes Are Highly Efficient and Specific Catalysts 79
An Enzyme’s Active Site Binds Substrates and Carries Out Catalysis 80
Serine Proteases Demonstrate How an Enzyme’s Active Site Works 81
Enzymes in a Common Pathway Are Often Physically Associated with One Another 84
Enzymes Called Molecular Motors Convert Energyinto Motion 85
3.4 Regulating Protein Function Ⅰ:Protein Degradation 86
Regulated Synthesis and Degradation of Proteins is a Fundamental Property of Cells 86
The Proteasome Is a Complex Molecular Machine Used to Degrade Proteins 87
Ubiquitin Marks Cytosolic Proteins for Degradation in Proteasomes 88
3.5 Regulating Protein Function Ⅱ:Noncovalent and Covalent Modifications 88
Noncovalent Binding Permits Allosteric,or Cooperative,Regulation of Proteins 89
Noncovalent Binding of Calcium and GTP Are Widely Used As Allosteric Switches to Control Protein Activity 90
Phosphorylation and Dephosphorylation Covalently Regulate Protein Activity 91
Proteolytic Cleavage Irreversibly Activates or Inactivates Some Proteins 91
Higher-Order Regulation Includes Control of Protein Location and Concentration 92
3.6 Purifying,Detecting,and Characterizing Proteins 92
Centrifugation Can Separate Particles and Molecules That Differ in Mass or Density 92
Electrophoresis Separates Molecules on the Basis of Their Charge-to-Mass Ratio 94
Liquid Chromatography Resolves Proteins by Mass,Charge,or Binding Affinity 96
Highly Specific Enzyme and Antibody Assays Can Detect Individual Proteins 98
Radioisotopes Are Indispensable Tools for Detecting Biological Molecules 99
Mass Spectrometry Can Determine the Mass and Sequence of Proteins 101
Protein Primary Structure Can Be Determined by Chemical Methods and from Gene Sequences 103
Protein Conformation Is Determined by Sophisticated Physical Methods 103
3.7 Proteomics 105
Proteomics Is the Study of All or a Large Subset of Proteins in a Biological System 105
Advanced Techniques in Mass Spectrometry Are Critical to Proteomic Analysis 106
Part Ⅱ Genetics and Molecular Biology 111
4 BASIC MOLECULAR GENETIC MECHANISMS 111
4.1 Structure of Nucleic Acids 113
A Nucleic Acid Strand Is a Linear Polymer with End-to-End Directionality 113
Native DNA Is a Double Helix of Complementary Antiparallel Strands 114
DNA Can Undergo Reversible Strand Separation 116
Torsional Stress in DNA Is Relieved by Enzymes 117
Different Types of RNA Exhibit Various Conformations Related to Their Functions 118
4.2 Transcription of Protein-Coding Genes and Formation of Functional mRNA 120
A Template DNA Strand Is Transcribed into a Complementary RNA Chain by RNA Polymerase 120
Organization of Genes Differs in Prokaryotic and Eukaryotic DNA 122
Eukaryotic Precursor mRNAs Are Processed to Form Functional mRNAs 123
Alternative RNA Splicing Increases the Number of Proteins Expressed from a Single Eukaryotic Gene 125
4.3 The Decoding of mRNA by tRNAs 127
Messenger RNA Carries information from DNA in a Three-Letter Genetic Code 127
The Folded Structure of tRNA Promotes Its Decoding Functions 129
Nonstandard Base Pairing Often Occurs Between Codons and Anticodons 130
Amino Acids Become Activated When Covalently Linked to tRNAs 131
4.4 Stepwise Synthesis of Proteins on Ribosomes 132
Ribosomes Are Protein-Synthesizing Machines 132
Methionyl-tRNAiMET Recognizes the AUG Start Codon 133
Translation Initiation Usually Occurs at the First AUG from the 5’ End of an mRNA 133
During Chain Elongation Each Incoming Aminoacyl-tRNA Moves Through Three Ribosomal Sites 135
Translation Is Terminated by Release Factors When a Stop Codon Is Reached 137
Polysomes and Rapid Ribosome Recycling Increase the Efficiency of Translation 138
4.5 DNA Replication 139
DNA Polymerases Require a Primer to Initiate Replication 140
Duplex DNA Is Unwound and Daughter Strands Are Formed at the DNA Replication Fork 141
Several Proteins Participate in DNA Replication 141
DNA Replication Usually Occurs Bidirectionally from Each Origin 143
4.6 DNA Repair and Recombination 145
DNA Polymerases Introduce Copying Errors and Also Correct Them 145
Chemical and Radiation Damage to DNA Can Lead to Mutations 145
High-Fidelity DNA Excision-Repair Systems Recognize and Repair Damage 147
Base Excision Repairs T·G Mismatches and Damaged Bases 147
Mismatch Excision Repairs Other Mismatches and Small Insertions and Deletions 147
Nucleotide Excision Repairs Chemical Adducts That Distort Normal DNA Shape 148
Two Systems Utilize Recombination to Repair Double-Strand Breaks in DNA 149
Homologous Recombination Can Repair DNA Damage and Generate Genetic Diversity 150
4.7 Viruses:Parasites of the Cellular Genetic System 154
Most Viral Host Ranges Are Narrow 154
Viral Capsids Are Regular Arrays of One or a Few Types of Protein 154
Viruses Can Be Cloned and Counted in Plaque Assays 155
Lytic Viral Growth Cycles Lead to the Death of Host Cells 156
Viral DNA Is Integrated into the Host-Cell Genome in Some Nonlytic Viral Growth Cycles 158
5 MOLECULAR GENETIC TECHNIQUES 165
5.1 Genetic Analysis of Mutations to Identify and Study Genes 166
Recessive and Dominant Mutant Alleles Generally Have Opposite Effects on Gene Function 166
Segregation of Mutations in Breeding Experiments Reveals Their Dominance or Recessivity 167
Conditional Mutations Can Be Used to Study Essential Genes in Yeast 170
Recessive Lethal Mutations in Diploids Can Be Identified by Inbreeding and Maintained in Heterozygotes 171
Complementation Tests Determine Whether Different Recessive Mutations Are in the Same Gene 171
Double Mutants Are Useful in Assessing the Order in Which Proteins Function 171
Genetic Suppression and Synthetic Lethality Can Reveal Interacting or Redundant Proteins 173
Genes Can Be Identified by Their Map Position on the Chromosome 174
5.2 DNA Cloning and Characterization 176
Restriction Enzymes and DNA Ligases Allow Insertion of DNA Fragments into Cloning Vectors 176
E.coli Plasmid Vectors Are Suitable for Cloning Isolated DNA Fragments 178
cDNA Libraries Represent the Sequences of Protein-Coding Genes 179
cDNAs Prepared by Reverse Transcription of Cellular mRNAs Can Be Cloned to Generate cDNA Libraries 181
DNA Libraries Can Be Screened by Hybridization to an Oligonucleotide Probe 181
Yeast Genomic Libraries Can Be Constructed with Shuttle Vectors and Screened by Functional Complementation 182
Gel Electrophoresis Allows Separation of Vector DNA from Cloned Fragments 184
Cloned DNA Molecules Are Sequenced Rapidly by the Dideoxy Chain-Termination Method 187
The Polymerase Chain Reaction Amplifies a Specific DNA Sequence from a Complex Mixture 188
5.3 Using Cloned DNA Fragments to Study Gene Expression 191
Hybridization Techniques Permit Detection of Specific DNA Fragments and mRNAs 191
DNA Microarrays Can Be Used to Evaluate the Expression of Many Genes at One Time 192
Cluster Analysis of Multiple Expression Experiments Identifies Co-regulated Genes 193
E.coli Expression Systems Can Produce Large Quantities of Proteins from Cloned Genes 194
Plasmid Expression Vectors Can Be Designed for Use in Animal Cells 196
5.4 Identifying and Locating Human Disease Genes 198
Many Inherited Diseases Show One of Three Major Patterns of Inheritance 199
DNA Polymorphisms Are Used in Linkage-Mapping Human Mutations 200
Linkage Studies Can Map Disease Genes with a Resolution of About 1 Centimorgan 201
Further Analysis Is Needed to Locate a Disease Gene in Cloned DNA 202
Many Inherited Diseases Result from Multiple Genetic Defects 203
5.5 Inactivating the Function of Specific Genes in Eukaryotes 204
Normal Yeast Genes Can Be Replaced with Mutant Alleles by Homologous Recombination 205
Transcription of Genes Ligated to a Regulated Promoter Can Be Controlled Experimentally 206
Specific Genes Can Be Permanently Inactivated in the Germ Line of Mice 207
Somatic Cell Recombination Can Inactivate Genes in Specific Tissues 208
Dominant-Negative Alleles Can Functionally Inhibit Some Genes 209
RNA Interference Causes Gene Inactivation by Destroying the Corresponding mRNA 210
6 GENES,GENOMICS,AND CHROMOSOMES 215
6.1 Eukaryotic Gene Structure 217
Most Eukaryotic Genes Contain Introns and Produce mRNAs Encoding Single Proteins 217
Simple and Complex Transcription Units Are Found in Eukaryotic Genomes 217
Protein-Coding Genes May Be Solitary or Belong to a Gene Family 219
Heavily Used Gene Products Are Encoded by Multiple Copies of Genes 221
Nonprotein-Coding Genes Encode Functional RNAs 222
6.2 Chromosomal Organization of Genes and Noncoding DNA 223
Genomes of Many Organisms Contain Much Nonfunctional DNA 223
Most Simple-Sequence DNAs Are Concentrated in Specific Chromosomal Locations 224
DNA Fingerprinting Depends on Differences in Length of Simple-Sequence DNAs 225
Unclassified Spacer DNA Occupies a Significant Portion of the Genome 225
6.3 Transposable(Mobile) DNA Elements 226
Movement of Mobile Elements Involves a DNA or an RNA Intermediate 226
DNA Transposons Are Present in Prokaryotes and Eukaryotes 227
LTR Retrotransposons Behave Like Intracellular Retroviruses 229
Non-LTR Retrotransposons Transpose by a Distinct Mechanism 230
Other Retrotransposed RNAs Are Found in Genomic DNA 234
Mobile DNA Elements Have Significantly Influenced Evolution 234
6.4 Organelle DNAs 236
Mitochondria Contain Multiple mtDNA Molecules 237
mtDNA Is Inherited Cytoplasmically 237
The Size,Structure,and Coding Capacity of mtDNA Vary Considerably Between Organisms 238
Products of Mitochondrial Genes Are Not Exported 240
Mitochondria Evolved from a Single Endosymbiotic Event Involving a Rickettsia-like Bacterium 240
Mitochondrial Genetic Codes Differ from the Standard Nuclear Code 240
Mutations in Mitochondrial DNA Cause Several Genetic Diseases in Humans 240
Chloroplasts Contain Large DNAs Often Encoding More Than a Hundred Proteins 242
6.5 Genomics:Genome-wide Analysis of Gene Structure and Expression 243
Stored Sequences Suggest Functions of Newly Identified Genes and Proteins 243
Comparison of Related Sequences from Different Species Can Give Clues to Evolutionary Relationships Among Proteins 244
Genes Can Be Identified Within Genomic DNA Sequences 244
The Number of Protein-Coding Genes in an Organism’s Genome Is Not Directly Related to Its Biological Complexity 245
Single Nucleotide Polymorphisms and Gene Copy-Number Variation Are Important Determinants of Differences Between Individuals of a Species 246
6.6 Structural Organization of Eukaryotic Chromosomes 247
Chromatin Exists in Extended and Condensed Forms 248
Modifications of Histone Tails Control Chromatin Condensation and Function 250
Nonhistone Proteins Provide a Structural Scaffold for Long Chromatin Loops 254
Additional Nonhistone Proteins Regulate Transcription and Replication 256
6.7 Morphology and Functional Elements of Eukaryotic Chromosomes 257
Chromosome Number,Size,and Shape at Metaphase Are Species-Specific 257
During Metaphase,Chromosomes Can Be Distinguished by Banding Patterns and Chromosome Painting 258
Chromosome Painting and DNA Sequencing Reveal the Evolution of Chromosomes 259
Interphase Polytene Chromosomes Arise by DNA Amplification 260
Three Functional Elements Are Required for Replication and Stable Inheritance of Chromosomes 261
Centromere Sequences Vary Greatly in Length 263
Addition of Telomeric Sequences by Telomerase Prevents Shortening of Chromosomes 263
7 TRANSCRIPTIONAL CONTROL OF GENE EXPRESSION 269
7.1 Control of Gene Expression in Bacteria 271
Transcription Initiation by Bacterial RNA Polymerase Requires Association with a Sigma Factor 271
Initiation of Iac Operon Transcription Can Be Repressed and Activated 271
Small Molecules Regulate Expression of Many Bacterial Genes via DNA-Binding Repressors and Activators 273
Transcription Initiation from Some Promoters Requires Alternative Sigma Factors 273
Transcription by σ54-RNA Polymerase Is Controlled by Activators That Bind Far from the Promoter 274
Many Bacterial Responses Are Controlled by Two-Component Regulatory Systems 275
7.2 Overview of Eukaryotic Gene Control and RNA Polymerases 276
Regulatory Elements in Eukaryotic DNA Are Found Both Close to and Many Kilobases Away from Transcription Start Sites 276
Three Eukaryotic Polymerases Catalyze Formation of Different RNAs 278
The Largest Subunit in RNA Polymerase Ⅱ Has an Essential Carboxyl-Terminal Repeat 279
RNA Polymerase Ⅱ Initiates Transcription at DNA Sequences Corresponding to the 5’ Cap of mRNAs 280
7.3 Regulatory Sequences in Protein-Coding Genes 282
The TATA Box,Initiators,and CpG Islands Function as Promoters in Eukaryotic DNA 282
Promoter-Proximal Elements Help Regulate Eukaryotic Genes 282
Distant Enhancers Often Stimulate Transcription by RNA Polymerase Ⅱ 284
Most Eukaryotic Genes Are Regulated by Multiple Transcription-Control Elements 285
7.4 Activators and Repressors of Transcription 286
Footprinting and Gel-Shift Assays Detect Protein-DNA Interactions 286
Activators Are Modular Proteins Composed of Distinct Functional Domains and Promote Transcription 288
Repressors Inhibit Transcription and Are the Functional Converse of Activators 290
DNA-Binding Domains Can Be Classified into Numerous Structural Types 290
Structurally Diverse Activation and Repression Domains Regulate Transcription 293
Transcription Factor Interactions Increase Gene-Control Options 294
Multiprotein Complexes Form on Enhancers 295
7.5 Transcription Initiation by RNA Polymerase Ⅱ 296
General Transcription Factors Position RNA Polymerase Ⅱ at Start Sites and Assist in Initiation 296
Sequential Assembly of Proteins Forms the Pol Ⅱ Transcription Preinitiation Complex in Vitro 297
In Vivo Transcription Initiation by Pol Ⅱ Requires Additional Proteins 298
7.6 Molecular Mechanisms of Transcription Repression and Activation 299
Formation of Heterochromatin Silences Gene Expression at Telomeres,Near Centromeres,and in Other Regions 299
Repressors Can Direct Histone Deacetylation and Methylation at Specific Genes 303
Activators Can Direct Histone Acetylation and Methylation at Specific Genes 305
Chromatin-Remodeling Factors Help Activate or Repress Transcription 306
Histone Modifications Vary Greatly in Their Stabilities 307
The Mediator Complex Forms a Molecular Bridge Between Activation Domains and Pol Ⅱ 307
Transcription of Many Genes Requires Ordered Binding and Function of Activators and Co-activators 308
The Yeast Two-Hybrid System Exploits Activator Flexibility to Detect cDNAs That Encode Interacting Proteins 310
7.7 Regulation of Transcription-Factor Activity 311
All Nuclear Receptors Share a Common Domain Structure 312
Nuclear-Receptor Response Elements Contain Inverted or Direct Repeats 313
Hormone Binding to a Nuclear Receptor Regulates Its Activity as a Transcription Factor 313
7.8 Regulated Elongation and Termination of Transcription 314
Transcription of the HIV Genome Is Regulated by an Antitermination Mechanism 315
Promoter-Proximal Pausing of RNA Polymerase Ⅱ Occurs in Some Rapidly Induced Genes 316
7.9 Other Eukaryotic Transcription Systems 316
Transcription Initiation by Pol Ⅰ and Pol Ⅲ Is Analogous to That by Pol Ⅱ 316
Mitochondrial and Chloroplast DNAs Are Transcribed by Organelle-Specific RNA Polymerases 317
8 POST-TRANSCRIPTIONAL GENE CONTROL 323
8.1 Processing of Eukaryotic Pre-mRNA 325
The 5’ Cap Is Added to Nascent RNAs Shortly After Transcription Initiation 325
A Diverse Set of Proteins with Conserved RNA-Binding Domains Associate with Pre-mRNAs 326
Splicing Occurs at Short,Conserved Sequences in Pre-mRNAs via Two Transesterification Reactions 329
During Splicing,snRNAs Base-Pair with Pre-mRNA 330
Spliceosomes,Assembled from snRNPs and a Pre-mRNA,Carry Out Splicing 330
Chain Elongation by RNA Polymerase Ⅱ Is Coupled to the Presence of RNA-Processing Factors 333
SR Proteins Contribute to Exon Definition in Long Pre-mRNAs 333
Self-Splicing Group Ⅱ Introns Provide Clues to the Evolution of snRNAs 334
3’ Cleavage and Polyadenylation of Pre-mRNAs Are Tightly Coupled 335
Nuclear Exonucleases Degrade RNA That Is Processed Out of Pre-mRNAs 336
8.2 Regulation of Pre-mRNA Processing 337
Alternative Splicing Is the Primary Mechanism for Regulating mRNA Processing 337
A Cascade of Regulated RNA Splicing Controls Drosophila Sexual Differentiation 338
Splicing Repressors and Activators Control Splicing at Alternative Sites 339
RNA Editing Alters the Sequences of Some Pre-mRNAs 340
8.3 Transport of mRNA Across the Nuclear Envelope 341
Nuclear Pore Complexes Control Import and Exportfrom the Nucleus 342
Pre-mRNAs in Spliceosomes Are Not Exported from the Nucleus 345
HIV Rev Protein Regulates the Transport of Unspliced Viral mRNAs 346
8.4 Cytoplasmic Mechanisms of Post-transcriptional Control 347
Micro RNAs Repress Translation of Specific mRNAs 347
RNA Interference Induces Degradation of Precisely Complementary mRNAs 349
Cytoplasmic Polyadenylation Promotes Translation of Some mRNAs 351
Degradation of mRNAs in the Cytoplasm Occurs by Several Mechanisms 352
Protein Synthesis Can Be Globally Regulated 353
Sequence-Specific RNA-Binding Proteins Control Specific mRNA Translation 356
Surveillance Mechanisms Prevent Translation of Improperly Processed mRNAs 357
Localization of mRNAs Permits Production of Proteins at Specific Regions Within the Cytoplasm 357
8.5 Processing of rRNA and tRNA 358
Pre-rRNA Genes Function as Nucleolar Organizers and Are Similar in All Eukaryotes 359
Small Nucleolar RNAs Assist in Processing Pre-rRNAs 360
Self-Splicing Group I Introns Were the First Examples of Catalytic RNA 363
Pre-tRNAs Undergo Extensive Modification in the Nucleus 363
Nuclear Bodies Are Functionally Specialized Nuclear Domains 364
Part Ⅲ Cell Structure and Function 371
9 VISUALIZING,FRACTIONATING,AND CULTURING CELLS 371
9.1 Organelles of the Eukaryotic Cell 372
The Plasma Membrane Has Many Common Functions in All Cells 372
Endosomes Take Up Soluble Macromolecules from the Cell Exterior 372
Lysosomes Are Acidic Organelles That Contain a Battery of Degradative Enzymes 373
Peroxisomes Degrade Fatty Acids and Toxic Compounds 374
The Endoplasmic Reticulum Is a Network of Interconnected Internal Membranes 375
The Golgi Complex Processes and Sorts Secreted and Membrane Proteins 376
Plant Vacuoles Store Small Molecules and Enable a Cell to Elongate Rapidly 377
The Nucleus Contains the DNA Genome,RNA Synthetic Apparatus,and a Fibrous Matrix 378
Mitochondria Are the Principal Sites of ATP Production in Aerobic Non photosynthetic Cells 378
Chloroplasts Contain Internal Compartments in Which Photosynthesis Takes Place 379
9.2 Light Microscopy:Visualizing Cell Structure and Localizing Proteins Within Cells 380
The Resolution of the Light Microscope Is About 0.2 μm 381
Phase-Contrast and Differential Interference Contrast Microscopy Visualize Unstained Living Cells 381
Fluorescence Microscopy Can Localize and Quantify Specific Molecules in Live Cells 382
Imaging Subcellular Details Often Requires that the Samples Be Fixed,Sectioned,and Stained 384
Immunofluorescence Microscopy Can Detect Specific Proteins in Fixed Cells 385
Confocal and Deconvolution Microscopy Enable Visualization of Three-Dimensional Objects 386
Graphics and Informatics Have Transformed Modern Microscopy 387
9.3 Electron Microscopy:Methods and Applications 388
Resolution of Transmission Electron Microscopy is Vastly Greater Than That of Light Microscopy 388
Cryoelectron Microscopy Allows Visualization of Particles Without Fixation or Staining 389
Electron Microscopy of Metal-Coated Specimens Can Reveal Surface Features of Cells and Their Components 390
9.4 Purification of Cell Organelles 391
Disruption of Cells Releases Their Organelles and Other Contents 391
Centrifugation Can Separate Many Types of Organelles 392
Organelle-Specific Antibodies Are Useful in Preparing Highly Purified Organelles 393
9.5 Isolation,Culture,and Differentiation of Metazoan Cells 394
Flow Cytometry Separates Different Cell Types 394
Culture of Animal Cells Requires Nutrient-Rich Media and Special Solid Surfaces 395
Primary Cell Cultures Can Be Used to Study Cell Differentiation 396
Primary Cell Cultures and Cell Strains Have a Finite Life Span 396
Transformed Cells Can Grow Indefinitely in Culture 397
Some Cell Lines Undergo Differentiation in Culture 398
Hybrid Cells Called Hybridomas Produce Abundant Monoclonal Antibodies 400
HAT Medium Is Commonly Used to Isolate Hybrid Cells 402
CLASSIC EXPERIMENT 9.1 Separating Organelles 407
10 BIOMEMBRANE STRUCTURE 409
10.1 Biomembranes:Lipid Composition and Structural Organization 411
Phospholipids Spontaneously Form Bilayers 411
Phospholipid Bilayers Form a Sealed Compartment Surrounding an Internal Aqueous Space 411
Biomembranes Contain Three Principal Classes of Lipids 415
Most Lipids and Many Proteins Are Laterally Mobile in Biomembranes 416
Lipid Composition Influences the Physical Properties of Membranes 418
Lipid Composition Is Different in the Exoplasmic and Cytosolic Leaflets 419
Cholesterol and Sphingolipids Cluster with Specific Proteins in Membrane Microdomains 420
10.2 Biomembranes:Protein Components and Basic Functions 421
Proteins Interact with Membranes in Three Different Ways 421
Most Transmembrane Proteins Have Membrane-Spanning α Helices 422
Multiple β Strands in Porins Form Membrane-Spanning “Barrels” 424
Covalently Attached Hydrocarbon Chains Anchor Some Proteins to Membranes 424
All Transmembrane Proteins and Glycolipids Are Asymmetrically Oriented in the Bilayer 426
Lipid-Binding Motifs Help Target Peripheral Proteins to the Membrane 427
Proteins Can Be Removed from Membranes by Detergents or High-Salt Solutions 427
10.3 Phospholipids,Sphingolipids,and Cholesterol:Synthesis and Intracellular Movement 429
Fatty Acids Synthesis Is Mediated by Several Important Enzymes 430
Small Cytosolic Proteins Facilitate Movement of Fatty Acids 430
Incorporation of Fatty Acids into Membrane Lipids Takes Place on Organelle Membranes 431
Flippases Move Phospholipids from One Membrane Leaflet to the Opposite Leaflet 431
Cholesterol Is Synthesized by Enzymes in the Cytosol and ER Membrane 432
Cholesterol and Phospholipids Are Transported Between Organelles by Several Mechanisms 433
11 TRANSMEMBRANE TRANSPORT OF IONS AND SMALL MOLECULES 437
11.1 Overview of Membrane Transport 438
Only Small Hydrophobic Molecules Cross Membranes by Simple Diffusion 438
Membrane Proteins Mediate Transport of Most Molecules and All Ions Across Biomembranes 439
11.2 Uniport Transport of Glucose and Water 441
Several Features Distinguish Uniport Transport from Simple Diffusion 441
GLUT1 Uniporter Transports Glucose into Most Mammalian Cells 442
The Human Genome Encodes a Family of Sugar-Transporting GLUT Proteins 443
Transport Proteins Can Be Enriched Within Artificial Membranes and Cells 443
Osmotic Pressure Causes Water to Move Across Membranes 444
Aquaporins Increase the Water Permeability of Cell Membranes 444
11.3 ATP-Powered Pumps and the Intracellular Ionic Environment 447
Different Classes of Pumps Exhibit Characteristic Structural and Functional Properties 447
ATP-Powered Ion Pumps Generate and Maintain Ionic Gradients Across Cellular Membranes 448
Muscle Relaxation Depends on Ca 2+ ATPases That Pump Ca 2+ from the Cytosol into the Sarcoplasmic Reticulum 449
Calmodulin Regulates the Plasma Membrane Ca 2+ Pumps That Control Cytosolic Ca 2+Concentrations 451
Na+/K+ ATPase Maintains the Intracellular Na+and K+ Concentrations in Animal Cells 452
V-Class H+ ATPases Maintain the Acidity of Lysosomes and Vacuoles 453
Bacterial Permeases Are ABC Proteins That Import a Variety of Nutrients from the Environment 454
The Approximately 50 Mammalian ABC Transporters Play Diverse and Important Roles in Cell and Organ Physiology 455
Certain ABC Proteins “Flip” Phospholipids and Other Lipid-Soluble Substrates from One Membrane Leaflet to the Opposite Leaflet 456
11.4 Nongated Ion Channels and the Resting Membrane Potential 458
Selective Movement of Ions Creates a Transmembrane Electric Potential Difference 458
The Membrane Potential in Animal Cells Depends Largely on Potassium Ion Movements Through Open Resting K+ Channels 460
Ion Channels Contain a Selectivity Filter Formed from Conserved Transmembrane Segments 461
Patch Clamps Permit Measurement of Ion Movements Through Single Channels 463
Novel Ion Channels Can Be Characterized by a Combination of Oocyte Expression and Patch Clamping 464
Na+ Entry into Mammalian Cells Has a Negative Change in Free Energy(△G) 464
11.5 Cotransport by Symporters and Antiporters 465
Na+-Linked Symporters Import Amino Acids and Glucose into Animal Cells Against High Concentration Gradients 466
Bacterial Symporter Structure Reveals the Mechanism of Substrate Binding 467
Na+-Linked Ca 2+ Antiporter Exports Ca 2+ from Cardiac Muscle Cells 468
Several Cotransporters Regulate Cytosolic pH 468
A Putative Cation Exchange Protein Plays a Key Role in Evolution of Human Skin Pigmentation 469
Numerous Transport Proteins Enable Plant Vacuoles to Accumulate Metabolites and Ions 469
11.6 Transepithelial Transport 470
Multiple Transport Proteins Are Needed to Move Glucose and Amino Acids Across Epithelia 471
Simple Rehydration Therapy Depends on the Osmotic Gradient Created by Absorption of Glucose and Na+ 471
Parietal Cells Acidify the Stomach Contents While Maintaining a Neutral Cytosolic pH 472
CLASSIC EXPERIMENT 11.1 Stumbling Upon Active Transport 477
12 CELLULAR ENERGETICS 479
12.1 First Steps of Glucose and Fatty Acid Catabolism:Glycolysis and the Citric Acid Cycle 480
During Glycolysis(Stage Ⅰ),Cytosolic Enzymes Convert Glucose to Pyruvate 481
The Rate of Glycolysis Is Adjusted to Meet the Cell’s Need for ATP 483
Glucose Is Fermented Under Anaerobic Conditions 485
Under Aerobic Conditions,Mitochondria Efficiently Oxidize Pyruvate and Generate ATP(Stages Ⅱ-Ⅳ) 485
Mitochondria Are Dynamic Organelles with Two Structurally and Functionally Distinct Membranes 485
In Stage Ⅱ,Pyruvate Is Oxidized to CO2 and High-Energy Electrons Stored in Reduced Coenzymes 487
Transporters in the Inner Mitochondrial Membrane Help Maintain Appropriate Cytosolic and Matrix Concentrations of NAD+ and NADH 489
Mitochondrial Oxidation of Fatty Acids Generates ATP 491
Peroxisomal Oxidation of Fatty Acids Generates No ATP 491
12.2 The Electron Transport Chain and Generation of the Proton-Motive Force 493
Stepwise Electron Transport Efficiently Releases the Energy Stored in NADH and FADH2 493
Electron Transport in Mitochondria Is Coupled to Proton Pumping 493
Electrons Flow from FADH2 and NADH to O2 Through Four Multiprotein Complexes 494
Reduction Potentials of Electron Carriers Favor Electron Flow from NADH to O2 499
Experiments Using Purified Complexes Established the Stoichiometry of Proton Pumping 499
The Q Cycle Increases the Number of Protons Translocated as Electrons Flow Through Complex Ⅲ 500
The Proton-Motive Force in Mitochondria Is Due Largely to a Voltage Gradient Across the Inner Membrane 502
Toxic By-products of Electron Transport Can Damage Cells 502
12.3 Harnessing the Proton-Motive Force for Energy-Requiring Processes 503
The Mechanism of ATP Synthesis Is Shared Among Bacteria,Mitochondria,and Chloroplasts 505
ATP Synthase Comprises Two Multiprotein Complexes Termed F0 and F1 505
Rotation of the F1 γ Subunit,Driven by Proton Movement Through F0,Powers ATP Synthesis 506
ATP-ADP Exchange Across the Inner Mitochondrial Membrane Is Powered by the Proton-Motive Force 509
Rate of Mitochondrial Oxidation Normally Depends on ADP Levels 510
Brown-Fat Mitochondria Use the Proton-Motive Force to Generate Heat 510
12.4 Photosynthesis and Light-Absorbing Pigments 511
Thylakoid Membranes in Chloroplasts Are the Sites of Photosynthesis in Plants 511
Three of the Four Stages in Photosynthesis Occur Only During Illumination 511
Each Photon of Light Has a Defined Amount of Energy 513
Photosystems Comprise a Reaction Center and Associated Light-Harvesting Complexes 514
Photoelectron Transport from Energized Reaction-Center Chlorophyll a Produces a Charge Separation 514
Internal Antenna and Light-Harvesting Complexes Increase the Efficiency of Photosynthesis 515
12.5 Molecular Analysis of Photosystems 517
The Single Photosystem of Purple Bacteria Generates a Proton-Motive Force but No O2 517
Linear Electron Flow Through Both Plant Photosystems,PSII and PSI,Generates a Proton-Motive Force,O2,and NADPH 519
An Oxygen-Evolving Complex Is Located on the Luminal Surface of the PSII Reaction Center 520
Cells Use Multiple Mechanisms to Protect Against Damage from Reactive Oxygen Species During Photoelectron Transport 521
Cyclic Electron Flow Through PSI Generates a Proton-Motive Force but No NADPH or O2 522
Relative Activities of Photosystems Ⅰ and Ⅱ Are Regulated 523
12.6 CO2 Metabolism During Photosynthesis 524
Rubisco Fixes CO2 in the Chloroplast Stroma 525
Synthesis of Sucrose Using Fixed CO2 Is Completed in the Cytosol 525
Light and Rubisco Activase Stimulate CO2 Fixation 525
Photorespiration,Which Competes with Photosynthesis,Is Reduced in Plants That Fix CO2 by the C4 Pathway 527
13 MOVING PROTEINS INTO MEMBRANES AND ORGANELLES 533
13.1 Translocation of Secretory Proteins Across the ER Membrane 535
A Hydrophobic N-Terminal Signal Sequence Targets Nascent Secretory Proteins to the ER 536
Cotranslational Translocation Is Initiated by Two GTP-Hydrolyzing Proteins 537
Passage of Growing Polypeptides Through the Translocon Is Driven by Energy Released During Translation 539
ATP Hydrolysis Powers Post-translational Translocation of Some Secretory Proteins in Yeast 540
13.2 Insertion of Proteins into the ER Membrane 542
Several Topological Classes of Integral Membrane Proteins Are Synthesized on the ER 543
Internal Stop-Transfer and Signal-Anchor Sequences Determine Topology of Single-Pass Proteins 544
Multipass Proteins Have Multiple Internal Topogenic Sequences 546
A Phospholipid Anchor Tethers Some Cell-Surface Proteins to the Membrane 547
The Topology of a Membrane Protein Often Can Be Deduced from Its Sequence 547
13.3 Protein Modifications,Folding,and Quality Control in the ER 549
A Preformed N-Linked Oligosaccharide Is Added to Many Proteins in the Rough ER 550
Oligosaccharide Side Chains May Promote Folding and Stability of Glycoproteins 552
Disulfide Bonds Are Formed and Rearranged by Proteins in the ER Lumen 552
Chaperones and Other ER Proteins Facilitate Folding and Assembly of Proteins 552
Improperly Folded Proteins in the ER Induce Expression of Protein-Folding Catalysts 555
Unassembled or Misfolded Proteins in the ER Are Often Transported to the Cytosol for Degradation 556
13.4 Sorting of Proteins to Mitochondria and Chloroplasts 557
Amphipathic N-Terminal Signal Sequences Direct Proteins to the Mitochondrial Matrix 558
Mitochondrial Protein Import Requires Outer-Membrane Receptors and Translocons in Both Membranes 558
Studies with Chimeric Proteins Demonstrate Important Features of Mitochondrial Import 560
Three Energy Inputs Are Needed to Import Proteins into Mitochondria 561
Multiple Signals and Pathways Target Proteins to Submitochondrial Compartments 561
Targeting of Chloroplast Stromal Proteins Is Similar to Import of Mitochondrial Matrix Proteins 565
Proteins Are Targeted to Thylakoids by Mechanisms Related to Translocation Across the Bacterial Inner Membrane 565
13.5 Sorting of Peroxisomal Proteins 567
Cytosolic Receptor Targets Proteins with an SKL Sequence at the C-Terminus into the Peroxisomal Matrix 567
Peroxisomal Membrane and Matrix Proteins Are Incorporated by Different Pathways 568
13.6 Transport into and out of the Nucleus 569
Large and Small Molecules Enter and Leave the Nucleus via Nuclear Pore Complexes 570
Importins Transport Proteins Containing Nuclear- Localization Signals into the Nucleus 571
Exportins Transport Proteins Containing Nuclear-ExportSignals out of the Nucleus 573
Most mRNAs Are Exported from the Nucleus by a Ran-Independent Mechanism 573
14 VESICULAR TRAFFIC,SECRETION,AND ENDOCYTOSIS 579
14.1 Techniques for Studying the Secretory Pathway 580
Transport of a Protein Through the Secretory Pathway Can Be Assayed in Living Cells 582
Yeast Mutants Define Major Stages and Many Components in Vesicular Transport 584
Cell-Free Transport Assays Allow Dissection of Individual Steps in Vesicular Transport 585
14.2 Molecular Mechanisms of Vesicular Traffic 586
Assembly of a Protein Coat Drives Vesicle Formation and Selection of Cargo Molecules 586
A Conserved Set of GTPase Switch Proteins Controls Assembly of Different Vesicle Coats 587
Targeting Sequences on Cargo Proteins Make Specific Molecular Contacts with Coat Proteins 588
Rab GTPases Control Docking of Vesicles on Target Membranes 589
Paired Sets of SNARE Proteins Mediate Fusion of Vesicles with Target Membranes 591
Dissociation of SNARE Complexes After Membrane Fusion Is Driven by ATP Hydrolysis 591
14.3 Early Stages of the Secretory Pathway 592
COPII Vesicles Mediate Transport from the ER to the Golgi 592
COPI Vesicles Mediate Retrograde Transport within the Golgi and from the Golgi to the ER 594
Anterograde Transport Through the Golgi Occurs by Cisternal Maturation 595
14.4 Later Stages of the Secretory Pathway 597
Vesicles Coated with Clathrin and/or Adapter Proteins Mediate Several Transport Steps 598
Dynamin Is Required for Pinching Off of Clathrin Vesicles 599
Mannose 6-Phosphate Residues Target Soluble Proteins to Lysosomes 600
Study of Lysosomal Storage Diseases Revealed Key Components of the Lysosomal Sorting Pathway 602
Protein Aggregation in the trans-Golgi May Function in Sorting Proteins to Regulated Secretory Vesicles 602
Some Proteins Undergo Proteolytic Processing After Leaving the trans-Golgi 603
Several Pathways Sort Membrane Proteins to the Apical or Basolateral Region of Polarized Cells 604
14.5 Receptor-Mediated Endocytosis 606
Cells Take Up Lipids from the Blood in the Form of Large,Well-Defined Lipoprotein Complexes 606
Receptors for Low-Density Lipoprotein and Other Ligands Contain Sorting Signals That Target Them for Endocytosis 608
The Acidic pH of Late Endosomes Causes Most Receptor-Ligand Complexes to Dissociate 610
The Endocytic Pathway Delivers Iron to Cells without Dissociation of the Receptor-Transferrin Complex in Endosomes 611
14.6 Directing Membrane Proteins and Cytosolic Materials to the Lysosome 612
Multivesicular Endosomes Segregate Membrane Proteins Destined for the Lysosomal Membrane from Proteins Destined for Lysosomal Degradation 612
Retroviruses Bud from the Plasma Membrane by a Process Similar to Formation of Multivesicular Endosomes 614
CLASSIC EXPERIMENT 14.1 Following a Protein Out of the Cell 621
15 CELL SIGNALING Ⅰ:SIGNAL TRANSDUCTION AND SHORT-TERM CELLULAR RESPONSES 623
15.1 From Extracellular Signal to Cellular Response 625
Signaling Cells Produce and Release Signaling Molecules 625
Signaling Molecules Can Act Locally or at a Distance 625
Binding of Signaling Molecules Activates Receptors on Target Cells 626
15.2 Studying Cell-Surface Receptors 627
Receptor Proteins Bind Ligands Specifically 627
The Dissociation Constant Is a Measure of the Affinity of a Receptor for Its Ligand 628
Binding Assays Are Used to Detect Receptors and Determine Their Affinities for Ligands 628
Maximal Cellular Response to a Signaling Molecule Usually Does Not Require Activation of All Receptors 629
Sensitivity of a Cell to External Signals Is Determined by the Number of Surface Receptors and Their Affinity for Ligand 631
Receptors Can Be Purified by Affinity Techniques 631
Receptors Are Frequently Expressed from Cloned Genes 631
15.3 Highly Conserved Components of Intracellular Signal-Transduction Pathways 632
GTP-Binding Proteins Are Frequently Used As On/Off Switches 633
Protein Kinases and Phosphatases are Employed in Virtually All Signaling Pathways 634
Second Messengers Carry and Amplify Signals from Many Receptors 634
15.4 General Elements of G Protein-Coupled Receptor Systems 635
G Protein-Coupled Receptors Are a Large and Diverse Family with a Common Structure and Function 635
G Protein-Coupled Receptors Activate Exchange of GTP for GDP on the α Subunit of a Trimeric G Protein 637
Different G Proteins Are Activated by Different GPCRs and In Turn Regulate Different Effector Proteins 639
15.5 G Protein-Coupled Receptors That Regulate Ion Channels 640
Acetylcholine Receptors in the Heart Muscle Activate a G Protein That Opens K+ Channels 641
Light Activates Gαt-Coupled Rhodopsins 641
Activation of Rhodopsin Induces Closing of cGMP-Gated Cation Channels 642
Rod Cells Adapt to Varying Levels of Ambient Light Because of Opsin Phosphorylation and Binding of Arrestin 644
15.6 G Protein-Coupled Receptors That Activate or Inhibit Adenylyl Cyclase 646
Adenylyl Cyclase Is Stimulated and Inhibited by Different Receptor-Ligand Complexes 646
Structural Studies Established How Gαs·GTP Binds to and Activates Adenylyl Cyclase 646
cAMP Activates Protein Kinase A by Releasing Catalytic Subunits 647
Glycogen Metabolism Is Regulated by Hormone-Induced Activation of Protein Kinase A 648
cAMP-Mediated Activation of Protein Kinase A Produces Diverse Responses in Different Cell Types 649
Signal Amplification Commonly Occurs in Many Signaling Pathways 650
Several Mechanisms Down-Regulate Signaling from G Protein-Coupled Receptors 651
Anchoring Proteins Localize Effects of cAMP to Specific Regions of the Cell 652
15.7 G Protein-Coupled Receptors That Activate Phospholipase C 653
Phosphorylated Derivatives of Inositol Are Important Second Messengers 654
Calcium Ion Release from the Endoplasmic Reticulum is Triggered by IP3 654
The Ca 2+/Calmodulin Complex Mediates Many Cellular Responses to External Signals 655
Diacylglycerol(DAG) Activates Protein Kinase C,Which Regulates Many Other Proteins 656
Signal-Induced Relaxation of Vascular Smooth Muscle Is Mediated by cGMP-Activated Protein Kinase G 656
15.8 Integrating Responses of Cells to Environmental Influences 657
Integration of Multiple Second Messengers Regulates Glycogenolysis 657
Insulin and Glucagon Work Together to Maintain a Stable Blood Glucose Level 658
CLASSIC EXPERIMENT 15.1 The Infancy of Signal Transduction—GTP Stimulation of cAMP Synthesis 663
16 CELL-SIGNALING Ⅱ:SIGNALING PATHWAYS THAT CONTROL GENE ACTIVITY 665
16.1 TGFβ Receptors and the Direct Activation of Smads 668
A TGFβ Signaling Molecule Is Formed by Cleavage of an Inactive Precursor 668
Radioactive Tagging Was Used to Identify TGFβ Receptors 669
Activated TGFβ Receptors Phosphorylate Smad Transcription Factors 670
Negative Feedback Loops Regulate TGFβ/Smad Signaling 671
Loss of TGFβ Signaling Plays a Key Role in Cancer 671
16.2 Cytokine Receptors and the JAK/STAT Pathway 672
Cytokines Influence Development of Many Cell Types 672
Cytokine Receptors Have Similar Structures and Activate Similar Signaling Pathways 673
JAK Kinases Activate STAT Transcription Factors 674
Complementation Genetics Revealed That JAK and STAT Proteins Transduce Cytokine Signals 677
Signaling from Cytokine Receptors Is Regulated by Negative Signals 678
Mutant Erythropoietin Receptor That Cannot Be Turned Off Leads to Increased Numbers of Erythrocytes 679
16.3 Receptor Tyrosine Kinases 679
Ligand Binding Leads to Phosphorylation and Activation of Intrinsic Kinase in RTKs 680
Overexpression of HER2,a Receptor Tyrosine Kinase,Occurs in Some Breast Cancers 680
Conserved Domains Are Important for Binding Signal-Transduction Proteins to Activated Receptors 682
Down-regulation of RTK Signaling Occurs by Endocytosis and Lysosomal Degradation 683
16.4 Activation of Ras and MAP Kinase Pathways 684
Ras,a GTPase Switch Protein,Cycles Between Active and Inactive States 685
Receptor Tyrosine Kinases Are Linked to Ras by Adapter Proteins 685
Genetic Studies in Drosophila Identified Key Signal-Transducing Proteins in the Ras/MAP Kinase Pathway 685
Binding of Sos Protein to Inactive Ras Causes a Conformational Change That Activates Ras 687
Signals Pass from Activated Ras to a Cascade of Protein Kinases 688
MAP Kinase Regulates the Activity of Many Transcription Factors Controlling Early-Response Genes 690
G Protein-Coupled Receptors Transmit Signals to MAP Kinase in Yeast Mating Pathways 691
Scaffold Proteins Separate Multiple MAP Kinase Pathways in Eukaryotic Cells 692
The Ras/MAP Kinase Pathway Can Induce Diverse Cellular Responses 693
16.5 Phosphoinositides as Signal Transducers 694
Phospholipase Cγ Is Activated by Some RTKs and Cytokine Receptors 694
Recruitment of PI-3 Kinase to Hormone-Stimulated Receptors Leads to Synthesis of Phosphorylated Phosphatidylinositols 694
Accumulation of PI 3-Phosphates in the Plasma Membrane Leads to Activation of Several Kinases 695
Activated Protein Kinase B Induces Many Cellular Responses 696
The PI-3 Kinase Pathway Is Negatively Regulated by PTEN Phosphatase 697
16.6 Activation of Gene Transcription by Seven-Spanning Cell-Surface Receptors 697
CREB Links cAMP and Protein Kinase A to Activation of Gene Transcription 698
GPCR-Bound Arrestin Activates Several Kinase Cascades 698
Wnt Signals Trigger Release of a Transcription Factor from Cytosolic Protein Complex 699
Hedgehog Signaling Relieves Repression of Target Genes 700
16.7 Pathways That Involve Signal-Induced Protein Cleavage 703
Degradation of an Inhibitor Protein Activates the NF-κB Transcription Factors 703
Ligand-Activated Notch Is Cleaved Twice,Releasing a Transcription Factor 705
Matrix Metal loproteases Catalyze Cleavage of Many Signaling Proteins from the Cell Surface 706
Inappropriate Cleavage of Amyloid Precursor Protein Can Lead to Alzheimer’s Disease 706
Regulated Intramembrane Proteolysis of SREBP Releases a Transcription Factor That Acts to Maintain Phospholipid and Cholesterol Levels 707
17 CELL ORGANIZATION AND MOVEMENT Ⅰ:MICROFILAMENTS 713
17.1 Microfilaments and Actin Structures 716
Actin Is Ancient,Abundant,and Highly Conserved 717
G-Actin Monomers Assemble into Long,Helical F-Actin Polymers 717
F-Actin Has Structural and Functional Polarity 718
17.2 Dynamics of Actin Filaments 718
Actin Polymerization in Vitro Proceeds in Three Steps 719
Actin Filaments Grow Faster at(+) Ends Than at(-) Ends 720
Actin Filament Treadmilling Is Accelerated by Profilin and Cofilin 721
Thymosin-β4 Provides a Reservoir of Actin for Polymerization 722
Capping Proteins Block Assembly and Disassembly at Actin Filament Ends 722
17.3 Mechanisms of Actin Filament Assembly 723
Formins Assemble Unbranched Filaments 723
The Arp2/3 Complex Nucleates Branched Filament Assembly 724
Intracellular Movements Can Be Powered by Actin Polymerization 726
Toxins That Perturb the Pool of Actin Monomers Are Useful for Studying Actin Dynamics 726
17.4 Organization of Actin-Based Cellular Structures 728
Cross-Linking Proteins Organize Actin Filaments into Bundles or Networks 728
Adaptor Proteins Link Actin Filaments to Membranes 728
17.5 Myosins:Actin-Based Motor Proteins 731
Myosins Have Head,Neck,and Tail Domains with Distinct Functions 732
Myosins Make Up a Large Family of Mechanochemical Motor Proteins 733
Conformational Changes in the Myosin Head Couple ATP Hydrolysis to Movement 736
Myosin Heads Take Discrete Steps Along Actin Filaments 736
Myosin V Walks Hand Over Hand Down an Actin Filament 737
17.6 Myosin-Powered Movements 738
Myosin Thick Filaments and Actin Thin Filaments in Skeletal Muscle Slide Past One Another During Contraction 738
Skeletal Muscle Is Structured by Stabilizing and Scaffolding Proteins 740
Contraction of Skeletal Muscle Is Regulated by Ca 2+ and Actin-Binding Proteins 740
Actin and Myosin Ⅱ Form Contractile Bundles in Nonmuscle Cells 741
Myosin-Dependent Mechanisms Regulate Contraction in Smooth Muscle and Nonmuscle Cells 742
Myosin-V-Bound Vesicles Are Carried Along Actin Filaments 743
17.7 Cell Migration:Signaling and Chemotaxis 745
Cell Migration Coordinates Force Generation with Cell Adhesion and Membrane Recycling 745
The Small GTP-Binding Proteins Cdc42,Rac,and Rho Control Actin Organization 747
Cell Migration Involves the Coordinate Regulation of Cdc42,Rac,and Rho 748
Migrating Cells Are Steered by Chemotactic Molecules 750
Chemotactic Gradients Induce Altered Phosphoinositide Levels Between the Front and Back of a Cell 750
CLASSIC EXPERIMENT 17.1 Looking at Muscle Contraction 755
18 CELL ORGANIZATION AND MOVEMENT Ⅱ:MICROTUBULES AND INTERMEDIATE FILAMENTS 757
18.1 Microtubule Structure and Organization 758
Microtubule Walls Are Polarized Structures Built from αβ-Tubulin Dimers 758
Microtubules Are Assembled from MTOCs to Generate Diverse Organizations 760
18.2 Microtubule Dynamics 762
Microtubules Are Dynamic Structures Due to Kinetic Differences at Their Ends 763
Individual Microtubules Exhibit Dynamic Instability 763
Localized Assembly and “Search-and-Capture” Help Organize Microtubules 766
Drugs Affecting Tubulin Polymerization Are Useful Experimentally and to Treat Diseases 766
18.3 Regulation of Microtubule Structure and Dynamics 767
Microtubules Are Stabilized by Side- and End-Binding Proteins 767
Microtubules Are Disassembled by End Binding and Severing Proteins 768
18.4 Kinesins and Dyneins:Microtubule- Based Motor Proteins 769
Organelles in Axons Are Transported Along Microtubules in Both Directions 769
Kinesin-1 Powers Anterograde Transport of Vesicles Down Axons Toward the(+) End of Microtubules 770
Kinesins Form a Large Protein Family with Diverse Functions 771
Kinesin-1 Is a Highly Processive Motor 772
Dynein Motors Transport Organelles Toward the(-)End of Microtubules 774
Kinesins and Dyneins Cooperate in the Transport of Organelles Throughout the Cell 775
18.5 Cilia and Flagella:Microtubule-Based Surface Structures 777
Eukaryotic Cilia and Flagella Contain Long Doublet Microtubules Bridged by Dynein Motors 777
Ciliary and Flagellar Beating Are Produced by Controlled Sliding of Outer Doublet Microtubules 778
Intraflagellar Transport Moves Material Up and Down Cilia and Flagella 779
Defects in Intraflagellar Transport Cause Disease by Affecting Sensory Primary Cilia 780
18.6 Mitosis 781
Mitosis Can Be Divided into Six Phases 782
Centrosomes Duplicate Early in the Cell Cycle in Preparation for Mitosis 783
The Mitotic Spindle Contains Three Classes of Microtubules 784
Microtubule Dynamics Increases Dramatically in Mitosis 784
Microtubules Treadmill During Mitosis 785
The Kinetochore Captures and Helps Transport Chromosomes 786
Duplicated Chromosomes Are Aligned by Motors and Treadmilling Microtubules 788
Anaphase A Moves Chromosomes to Poles by Microtubule Shortening 789
Anaphase B Separates Poles by the Combined Action of Kinesins and Dynein 789
Additional Mechanisms Contribute to Spindle Formation 789
Cytokinesis Splits the Duplicated Cell in Two 789
Plant Cells Reorganize Their Microtubules and Build a New Cell Wall in Mitosis 790
18.7 Intermediate Filaments 791
Intermediate Filaments Are Assembled from Subunit Dimers 792
Intermediate Filaments Proteins Are Expressed in a Tissue-Specific Manner 792
Intermediate Filaments Are Dynamic 795
Defects in Lamins and Keratins Cause Many Diseases 795
18.8 Coordination and Cooperation between Cytoskeletal Elements 796
Intermediate Filament-Associated Proteins Contribute to Cellular Organization 796
Microfilaments and Microtubules Cooperate to Transport Melanosomes 796
Cdc42 Coordinates Microtubules and Microfilaments During Cell Migration 797
19 INTEGRATING CELLS INTO TISSUES 801
19.1 Cell-Cell and Cell-Matrix Adhesion:An Overview 803
Cell-Adhesion Molecules Bind to One Another and to Intracellular Proteins 803
The Extracellular Matrix Participates in Adhesion,Signaling,and Other Functions 805
The Evolution of Multifaceted Adhesion Molecules Enabled the Evolution of Diverse Animal Tissues 807
19.2 Cell-Cell and Cell-ECM Junctions and Their Adhesion Molecules 808
Epithelial Cells Have Distinct Apical,Lateral,and Basal Surfaces 808
Three Types of Junctions Mediate Many Cell-Cell and Cell-ECM Interactions 809
Cadherins Mediate Cell-Cell Adhesions in Adherens Junctions and Desmosomes 810
Tight Junctions Seal Off Body Cavities and Restrict Diffusion of Membrane Components 814
Integrins Mediate Cell-ECM Adhesions in Epithelial Cells 816
Gap Junctions Composed of Connexins Allow Small Molecules to Pass Directly Between Adjacent Cells 817
19.3 The Extracellular Matrix Ⅰ:The Basal Lamina 820
The Basal Lamina Provides a Foundation for Assembly of Cells into Tissues 820
Laminin,a Multiadhesive Matrix Protein,Helps Cross-link Components of the Basal Lamina 821
Sheet-Forming Type Ⅳ Collagen Is a Major Structural Component of the Basal Lamina 821
Perlecan,a Proteoglycan,Cross-links Components of the Basal Lamina and Cell-Surface Receptors 824
19.4 The Extracellular Matrix Ⅱ:Connective and Other Tissues 825
Fibrillar Collagens Are the Major Fibrous Proteins in the ECM of Connective Tissues 825
Fibrillar Collagen Is Secreted and Assembled into Fibrils Outside of the Cell 826
Type Ⅰ and Ⅱ Collagens Associate with Nonfibrillar Collagens to Form Diverse Structures 826
Proteoglycans and Their Constituent GAGs Play Diverse Roles in the ECM 827
Hyaluronan Resists Compression,Facilitates Cell Migration,and Gives Cartilage Its Gel-like Properties 829
Fibronectins Interconnect Cells and Matrix,Influencing Cell Shape,Differentiation,and Movement 830
19.5 Adhesive Interactions in Motile and Nonmotile Cells 833
Integrins Relay Signals Between Cells and Their Three-Dimensional Environment 833
Regulation of Integrin-Mediated Adhesion and Signaling Controls Cell Movement 834
Connections Between the ECM and Cytoskeleton Are Defective in Muscular Dystrophy 835
IgCAMs Mediate Cell-Cell Adhesion in Neuronal and Other Tissues 836
Leukocyte Movement into Tissues Is Orchestrated by a Precisely Timed Sequence of Adhesive Interactions 837
19.6 Plant Tissues 839
The Plant Cell Wall Is a Laminate of Cellulose Fibrils in a Matrix of Glycoproteins 840
Loosening of the Cell Wall Permits Plant Cell Growth 840
Plasmodesmata Directly Connect the Cytosols of Adjacent Cells in Higher Plants 840
Only a Few Adhesive Molecules Have Been Identified in Plants 841
Part Ⅳ Cell Growth and Development 847
20 REGULATING THE EUKARYOTIC CELL CYCLE 847
20.1 Overview of the Cell Cycle and Its Control 849
The Cell Cycle Is an Ordered Series of Events Leading to Cell Replication 849
Regulated Protein Phosphorylation and Degradation Control Passage Through the Cell Cycle 849
Diverse Experimental Systems Have Been Used to Identify and Isolate Cell-Cycle Control Proteins 851
20.2 Control of Mitosis by Cyclins and MPF Activity 853
Maturation-Promoting Factor(MPF) Stimulates Meiotic Maturation in Oocytes and Mitosis in Somatic Cells 854
Mitotic Cyclin Was First Identified in Early Sea Urchin Embryos 856
Cyclin B Levels and Kinase Activity of Mitosis-Promoting Factor(MPF) Change Together in Cycling Xenopus Egg Extracts 856
Anaphase-Promoting Complex(APC/C) Controls Degradation of Mitotic Cyclins and Exit from Mitosis 858
20.3 Cyclin-Dependent Kinase Regulation During Mitosis 859
MPF Components Are Conserved Between Lower and Higher Eukaryotes 860
Phosphorylation of the CDK Subunit Regulates the Kinase Activity of MPF 861
Conformational Changes Induced by Cyclin Binding and Phosphorylation Increase MPF Activity 862
20.4 Molecular Mechanisms for Regulating Mitotic Events 864
Phosphorylation of Nuclear Lamins and Other Proteins Promotes Early Mitotic Events 864
Unlinking of Sister Chromatids Initiates Anaphase 867
Chromosome Decondensation and Reassembly of the Nuclear Envelope Depend on Dephosphorylation of MPF Substrates 870
20.5 Cyclin-CDK and Ubiquitin-Protein Ligase Control of S phase 872
A Cyclin-Dependent Kinase(CDK) Is Critical for S-Phase Entry in S.cerevisiae 872
Three G1 Cyclins Associate with S.cerevisiae CDK to Form S-Phase-Promoting Factors 874
Degradation of the S-Phase Inhibitor Triggers DNA Replication 876
Multiple Cyclins Regulate the Kinase Activity of S.cerevisiae CDK During Different Cell-Cycle Phases 877
Replication at Each Origin Is Initiated Only Once During the Cell Cycle 877
20.6 Cell-Cycle Control in Mammalian Cells 879
Mammalian Restriction Point Is Analogous to START in Yeast Cells 880
Multiple CDKs and Cyclins Regulate Passage of Mammalian Cells Through the Cell Cycle 881
Regulated Expression of Two Classes of Genes Returns G0 Mammalian Cells to the Cell Cycle 881
Passage Through the Restriction Point Depends on Phosphorylation of the Tumor-Suppressor Rb Protein 882
Cyclin A Is Required for DNA Synthesis and CDK1 for Entry into Mitosis 883
Two Types of Cyclin-CDK Inhibitors Contribute to Cell-Cycle Control in Mammals 883
20.7 Checkpoints in Cell-Cycle Regulation 884
The Presence of Unreplicated DNA Prevents Entry into Mitosis 888
Improper Assembly of the Mitotic Spindle Prevents the Initiation of Anaphase 888
Proper Segregation of Daughter Chromosomes Is Monitored by the Mitotic Exit Network 889
Cell-Cycle Arrest of Cells with Damaged DNA Depends on Tumor Suppressors 891
20.8 Meiosis:A Special Type of Cell Division 892
Key Features Distinguish Meiosis from Mitosis 892
Repression of G1 Cyclins and a Meiosis-Specific Protein Kinase Promote Premeiotic S Phase 895
Recombination and a Meiosis-Specific Cohesin Subunit Are Necessary for the Specialized Chromosome Segregation in Meiosis
- 《治理、政治与国家=GOVERNANCE》POLITICS AND THE STATE
- 《暗黑之门 历任首相主导下的英国情报史话=SPIES》SECRET INTELLIGENCE AND BRITISH PRIME MINISTERS
- 《石像、神庙与失落的文明:改写世界文明史的玛雅发现之旅=THE EXTRAORDINARY JOUMEY OF JOHN L.STEPHENS AND FREDERICK CSTHERW》AND THE DISCOVERY OF THE LOST CIVILIZATION OF THE MAYA
- 《中国影视娱乐合同范本与风险防范=Chinas Film》Television and Entertainment Industry Contract Model and Risk Prevention
- 《政治观念史稿·卷一 希腊化、罗马和早期基督教=HISTORY OF POLITICAL IDEAS(VOLUMR 1) HELLENISM》ROME AND EARLY CHRISTIANITY
- 《PIANO ADVENTURES THE BASIC PIANO METHOD LEVEL 3B LESSON BOOK 2ND EDITION》NANCY AND RANDALL FABER 2015
- 《MOONSHOTS IN EDUCATION LAUNCHING BLENDED LEARNING IN THE COASSROOM》ESTHER WOJCICKI AND LANCE LZUMI 2015
- 《CHINAS NEW URBANIZATION DEVELOPMENTAL PATHS》 BLUEPRINTS AND PATTERNS SCIE
- 《DREAM FOR SOLO PERCUSIONIST (CROTALES》 VIBRAPHONE AND JOHN
- 《美国教育法与判例》秦梦群著=American public school law and court cases 2004
- 《你也可以创造生命的奇迹 来自全球的自我疗愈实证与方法 miraculous moments and extraordinary stories from people all over the w》露易丝·贺(Louise L. Hay)著 2012
- 《“中国印”的世界 骆芃芃篆刻书法艺术展作品集 the collection of exhibition of seal engraving and calligraphic works》骆芃芃著 2012
- 《THE CASE-STUDY METHOD IN PSYCHOLOGY AND RELATED DISCIPLINES》 1986
- 《DETECTION AND SPECTROMETRY OF FAINT LIGHT》JOHN MEABURN
- 《片上与无线网络技术=ON-CHIP AND WIRELESS NETWORK》王俊辉 2019
- 《被算法操控的生活:重新定义精准广告、大数据和AI=OUTNUMBERED FROM FACEBOOK AND GOOGLE TO FAKE NEWS AND FILTER-BUBBL》(瑞典)大卫·萨普特(DavidSumpter) 2020
- 《太空战:战略、原则与政策=SPACE WARFARE:STRATEGY PRINCIPLES AND POLICY》(美)约翰·J·克莱恩著 2019
- 《STM32嵌入式技术应用开发全案例实践=CASES PRACTICE OF STM32 EMBEDDED TECHNOLOGY APPLICATION AND DEVELOPMENT》苏李果 2020
- 《遥感抽样原理与应用=Principles and Applications of Remote Sensing Sampling》朱秀芳 2019
- 《纳米科学技术及应用=NANO SCIENCE & TECHNOLOGY AND APPLICATION》袁哲俊 2019