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E-raamat: Molecular Switch: Signaling and Allostery

  • Formaat: 440 pages
  • Ilmumisaeg: 01-Sep-2020
  • Kirjastus: Princeton University Press
  • Keel: eng
  • ISBN-13: 9780691200255
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  • Formaat: 440 pages
  • Ilmumisaeg: 01-Sep-2020
  • Kirjastus: Princeton University Press
  • Keel: eng
  • ISBN-13: 9780691200255

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A signature feature of living organisms is their ability to carry out purposeful actions by taking stock of the world around them. To that end, cells have an arsenal of signaling molecules linked together in signaling pathways, which switch between inactive and active conformations. The Molecular Switch articulates a biophysical perspective on signaling, showing how allostery—a powerful explanation of how molecules function across all biological domains—can be reformulated using equilibrium statistical mechanics, applied to diverse biological systems exhibiting switching behaviors, and successfully unify seemingly unrelated phenomena.

Rob Phillips weaves together allostery and statistical mechanics via a series of biological vignettes, each of which showcases an important biological question and accompanying physical analysis. Beginning with the study of ligand-gated ion channels and their role in problems ranging from muscle action to vision, Phillips then undertakes increasingly sophisticated case studies, from bacterial chemotaxis and quorum sensing to hemoglobin and its role in mammalian physiology. He looks at G-protein coupled receptors as well as the role of allosteric molecules in gene regulation. Phillips concludes by surveying problems in biological fidelity and offering a speculative chapter on the relationship between allostery and biological Maxwell demons.

Appropriate for graduate students and researchers in biophysics, physics, engineering, biology, and neuroscience, The Molecular Switch presents a unified, quantitative model for describing biological signaling phenomena.

Preface xiii
PART I THE MAKING OF MOLECULAR SWITCHES
1(74)
1 It's An Allosteric World
3(32)
1.1 The Second Secret of Life
3(1)
1.2 The Broad Reach of the Allostery Concept
4(10)
1.2.1 Sculpting Biochemistry via Allostery
5(4)
1.2.2 One- and Two-Component Signal Transduction and the Two-State Philosophy
9(5)
1.3 Reasoning about Feedback: The Rise of Allostery
14(6)
1.3.1 The Puzzle
14(3)
1.3.2 The Resolution of the Molecular Feedback Puzzle
17(3)
1.3.3 Finding the Allosterome
20(1)
1.4 Mathematicizing the Two-State Paradigm
20(8)
1.4.1 Transcendent Concepts in Physics
22(3)
1.4.2 One Equation to Rule Them All
25(3)
1.5 Beyond the MWC Two-State Concept
28(2)
1.5.1 Molecular Agnosticism: MWC versus KNF versus Eigen
28(2)
1.6 On Being Wrong
30(1)
1.7 Summary
31(1)
1.8 Further Reading
32(1)
1.9 References
33(2)
2 The Allosterician's Toolkit
35(40)
2.1 A Mathematical Microscope: Statistical Mechanics Preliminaries
35(9)
2.1.1 Microstates
36(2)
2.1.2 The Fundamental Law of Statistical Mechanics
38(2)
2.1.3 The Dimensionless Numbers of Thermal Physics
40(4)
2.1.4 Boltzmann and Probabilities
44(1)
2.2 Case Study in Statistical Mechanics: Ligand-Receptor Binding
44(5)
2.2.1 Ligand Binding and the Lattice Model of Solutions
45(4)
2.3 Conceptual Tools of the Trade: Free Energy and Entropy
49(5)
2.3.1 Resetting Our Zero of Energy Using the Chemical Potential
51(3)
2.4 The MWC Concept in Statistical Mechanical Language
54(3)
2.5 Cooperativity and Allostery
57(6)
2.5.1 Cooperativity and Hill Functions
59(2)
2.5.2 Cooperativity in the MWC Model
61(2)
2.6 Internal Degrees of Freedom and Ensemble Allostery
63(7)
2.7 Beyond Equilibrium
70(3)
2.8 Summary
73(1)
2.9 Further Reading
73(1)
2.10 References
74(1)
PART II THE LONG REACH OF ALLOSTERY
75(270)
3 Signaling At The Cell Membrane: Ion Channels
77(47)
3.1 How Cells Talk to the World
77(1)
3.2 Biological Processes and Ion Channels
78(3)
3.3 Ligand-Gated Channels
81(3)
3.4 Statistical Mechanics of the MWC Channel
84(10)
3.5 Data Collapse, Natural Variables, and the Bohr Effect
94(4)
3.5.1 Data Collapse and the Ion-Channel Bohr Effect
95(3)
3.6 Rate Equation Description of Channel Gating
98(8)
3.7 Cyclic Nucleotide--Gated Channels
106(6)
3.8 Beyond the MWC Model in Ion Channelology
112(9)
3.8.1 Conductance Substates and Conformational Kinetics
113(2)
3.8.2 The Koshland-Nemethy-Filmer Model Revealed
115(3)
3.8.3 Kinetic Proliferation
118(2)
3.8.4 The Question of Inactivation
120(1)
3.9 Summary
121(1)
3.10 Further Reading
121(1)
3.11 References
122(2)
4 How Bacteria Navigate The World Around Them
124(46)
4.1 Bacterial Information Processing
124(3)
4.1.1 Engelmanns Experiment and Bacterial Aerotaxis
124(1)
4.1.2 Love Thy Neighbors: Signaling between Bacteria
125(2)
4.2 Bacterial Chemotaxis
127(8)
4.2.1 The Chemotaxis Phenomenon
127(2)
4.2.2 Wiring Up Chemotaxis through Molecular Switching
129(6)
4.3 MWC Models of Chemotactic Response
135(11)
4.3.1 MWC Model of Chemotaxis Receptor Clusters
139(4)
4.3.2 Heterogenous Clustering
143(2)
4.3.3 Putting It All Together by Averaging
145(1)
4.4 The Amazing Phenomenon of Physiological Adaptation
146(9)
4.4.1 Adaptation by Hand
151(2)
4.4.2 Data Collapse in Chemotaxis
153(2)
4.5 Beyond the MWC Model in Bacterial Chemotaxis
155(1)
4.5 The Ecology and Physiology of Quorum Sensing
156(10)
4.6.1 Wiring Up Quorum Sensing
158(2)
4.6.2 Dose-Response Curves in Quorum Sensing
160(2)
4.6.3 Statistical Mechanics of Membrane Receptors
162(2)
4.6.4 Statistical Mechanics of Membrane Receptors with Inhibitors
164(1)
4.6.5 Data Collapse in Quorum Sensing
165(1)
4.7 Summary
166(1)
4.8 Further Reading and Viewing
166(2)
4.9 References
168(2)
5 The Wonderful World Of G Proteins And G Protein--Coupled Receptors
170(31)
5.1 The Biology of Color
171(6)
5.1.1 Crypsis in Field Mice
171(2)
5.1.2 Coat Color and GPCRs
173(4)
5.2 The G Protein-Coupled Receptor Paradigm
177(1)
5.3 Paradigmatic Examples of GPCRs
177(15)
5.3.1 The β-Adrenergic Receptor
179(4)
5.3.2 Vision, Rhodopsin, and Signal Transduction
183(4)
5.3.3 Light as a Ligand: Optogenetics
187(5)
5.4 G Protein--Coupled Ion Channels
192(6)
5.5 Summary
198(1)
5.6 Further Reading and Viewing
198(1)
5.7 References
199(2)
6 Dynamics Of Mwc Molecules: Enzyme Action And Allostery
201(30)
6.1 Enzyme Phenomenology
201(4)
6.2 Statistical Mechanics of Michaelis-Menten Enzymes
205(4)
6.3 Statistical Mechanics of MWC Enzymes
209(13)
6.3.1 Modulating Enzyme Activity with Allosteric Effectors
213(4)
6.3.2 Competitive Inhibitors and Enzyme Action
217(3)
6.3.3 Multiple Substrate Binding Sites
220(1)
6.3.4 What the Data Say
221(1)
6.4 Glycolysis and Allostery
222(6)
6.4.1 The Case of Phosphofructokinase
223(5)
6.5 Summary
228(1)
6.6 Further Reading
229(1)
6.7 References
230(1)
7 Hemoglobin, Nature's Honorary Enzyme
231(41)
7.1 Hemoglobin Claims Its Place in Science
231(8)
7.1.1 Hemoglobin and Respiration
232(3)
7.1.2 A Historical Interlude on the Colouring Matter
235(1)
7.1.3 Hemoglobin as a "Document of Evolutionary History"
236(3)
7.2 States and Weights and Binding Curves
239(5)
7.3 Y oh Y
244(2)
7.4 Hemoglobin and Effectors: The Bohr Effect and Beyond
246(6)
7.5 Physiological versus Evolutionary Adaptation: High Fliers and Deep Divers
252(7)
7.6 Hemoglobin and Competitors: Carbon Monoxide Fights Oxygen
259(5)
7.7 Pushing the MWC Framework Harder: Hemoglobin Kinetics
264(4)
7.8 Summary
268(1)
7.9 Further Reading
269(1)
7.10 References
270(2)
8 How Cells Decide What To Be: Signaling And Gene Regulation
272(31)
8.1 Of Repressors, Activators, and Allostery
273(4)
8.2 Thermodynamic Models of Gene Expression
277(7)
8.3 Induction of Genes
284(6)
8.4 Activation
290(9)
8.4.1 Binding of Inducer to Activator
291(3)
8.4.2 Binding of Activator to DNA
294(3)
8.4.3 Activation and Gene Expression
297(2)
8.5 Janus Factors
299(1)
8.6 Summary
300(1)
8.7 Further Reading
301(1)
8.8 References
302(1)
9 Building Logic From Allostery
303(13)
9.1 Combinatorial Control and Logic Gates
303(3)
9.2 Using MWC to Build Gates
306(5)
9.2.1 Making Logic
307(2)
9.2.2 A Tour of Parameter Space
309(2)
9.3 Beyond Two-Input Logic
311(3)
9.4 Summary
314(1)
9.5 Further Reading
315(1)
10 Dna Packing And Access: The Physics Of Combinatorial Control
316(29)
10.1 Genome Packing and Accessibility
316(2)
10.2 The Paradox of Combinatorial Control and Genomic Action at a Distance
318(2)
10.3 Nucleosomes and DNA Accessibility
320(10)
10.3.1 Equilibrium Accessibility of Nucleosomal DNA
324(6)
10.4 MWC Model of Nucleosomes: Arbitrary Number of Binding Sites
330(4)
10.5 Nucleosome Modifications and the Analogy with the Bohr Effect
334(2)
10.6 Stepping Up in Scales: A Toy Model of Combinatorial Control at Enhancers
336(4)
10.7 An Application of the MWC Model of Nucleosomes to Embryonic Development
340(2)
10.8 Summary
342(1)
10.9 Further Reading
343(1)
10.10 References
343(2)
PART III BEYOND ALLOSTERY
345(64)
11 Allostery Extended
347(18)
11.1 Ensemble Allostery
347(8)
11.1.1 Normal Modes and Mechanisms of Action at a Distance
349(2)
11.1.2 Integrating Out Degrees of Freedom
351(4)
11.2 Ensemble Allostery through Tethering
355(6)
11.2.1 Biochemistry on a Leash
355(2)
11.2.2 Random-Walk Models of Tethers
357(4)
11.3 Irreversible Allostery
361(1)
11.4 Summary
362(2)
11.5 Further Reading
364(1)
11.6 References
364(1)
12 Maxwell Demons, Proofreading, And Allostery
365(30)
12.1 Demonic Biology
365(1)
12.2 A Panoply of Demonic Behaviors in the Living World
366(17)
12.2.1 The Demon and Biological Specificity
368(5)
12.2.2 Making Stuff Happen in the Right Order
373(3)
12.2.3 The Free-Energy Cost of Demonic Behavior
376(7)
12.3 Overcoming Thermodynamics in Biology: Kinetic Proofreading
383(9)
12.3.1 Equilibrium Discrimination Is Not Enough
383(2)
12.3.2 The Hopfield-Ninio Mechanism
385(1)
12.3.3 Proofreading Goes Steampunk: Building Proofreading Engines
386(6)
12.4 Summary
392(1)
12.5 Further Reading
392(1)
12.6 References
393(2)
13 A Farewell To Allostery
395(14)
13.1 Diversity and Unity: Diverging and Converging Views of Biology
396(5)
13.2 Shortcomings of the Approach
401(4)
13.3 Beyond Allostery
405(1)
13.4 Further Reading
406(1)
13.5 References
407(2)
Index 409
Rob Phillips is the Fred and Nancy Morris Professor of Biophysics and Biology at the California Institute of Technology. He is the author of Crystals, Defects and Microstructures and coauthor of Physical Biology of the Cell and Cell Biology by the Numbers.