Protein and Peptide Folding, Misfolding, and Non-Folding

Herausgegeben von Schweitzer-Stenner, Reinhard; Uversky, Vladimir

• Gebundenes Buch

Produktbeschreibung

This book provides an overview on what researchers have learned about unfolded peptides and how this knowledge facilitates the understanding of (a) the folding process, (b) the binding of ligands to receptor molecules, and (c) peptide self-aggregation. In this context, different experimental, theoretical, and computational concepts and approaches are introduced. This book can become a very useful addition for graduate-level courses on protein folding for the education of undergraduate and graduate students in research groups, which are exploring peptide self-aggregation for biomedical and biotechnological purposes. Sheds new light on intrinsically disordered proteins and peptides, including their role in neurodegenerative diseases
With the discovery of intrinsically disordered proteins and peptides (IDPs), researchers realized that proteins do not necessarily adopt a well defined secondary and tertiary structure in order to perform biological functions. In fact, IDPs play biologically relevant roles, acting as inhibitors, scavengers, and even facilitating DNA/RNA-protein interactions. Due to their propensity for self-aggregation and fibril formation, some IDPs are involved in neurodegenerative diseases such as Parkinson's and Alzheimer's.
With contributions from leading researchers, this text reviews the most recent studies, encapsulating our understanding of IDPs. The authors explain how the growing body of IDP research is building our knowledge of the folding process, the binding of ligands to receptor molecules, and peptide self-aggregation. Readers will discover a variety of experimental, theoretical, and computational approaches used to better understand the properties and function of IDPs. Moreover, they'll discover the role of IDPs in human disease and as drug targets.
Protein and Peptide Folding, Misfolding, and Non-Folding begins with an introduction that explains why research on IDPs has significantly expanded in the past few years. Next, the book is divided into three sections:
Conformational Analysis of Unfolded States
Disordered Peptides and Molecular Recognition
Aggregation of Disordered Peptides
Throughout the book, detailed figures help readers understand the structure, properties, and function of IDPs. References at the end of each chapter serve as a gateway to the growing body of literature in the field.
With the publication of Protein and Peptide Folding, Misfolding, and Non-Folding, researchers now have a single place to discover IDPs, their diverse biological functions, and the many disciplines that have contributed to our evolving understanding of them.

Produktdetails

• Wiley Series in Protein and Peptide Science
• Verlag: Wiley & Sons
• 1. Auflage
• Seitenzahl: 576
• Erscheinungstermin: 27. März 2012
• Englisch
• Abmessung: 240mm x 161mm x 36mm
• Gewicht: 984g
• ISBN-13: 9780470591697
• ISBN-10: 0470591692
• Artikelnr.: 33381021

Autorenporträt

Reinhard Schweitzer-Stenner, PhD, is Professor and currently the Head of the Chemistry Department at Drexel University. Dr. Schweitzer-Stenner also heads the biospectroscopy research group. His research investigates peptide structure and functionally relevant heme distortions as well as ligand-receptor binding on the surface of mast cells. With more than 150 published research articles, Dr. Schweitzer-Stenner is widely recognized as a leader and pioneer in the study of the conformational properties of unfolded peptides.

Inhaltsangabe

Introduction to the Wiley Series on Protein and Peptide Science xiii Preface xv Contributors xix INTRODUCTION 1 1 Why Are We Interested in the Unfolded Peptides and Proteins? 3 Vladimir N. Uversky and A. Keith Dunker 1.1 Introduction
3 1.2 Why Study IDPs?
4 1.3 Lesson 1: Disorderedness Is Encoded in the Amino Acid Sequence and Can Be Predicted
5 1.4 Lesson 2: Disordered Proteins Are Highly Abundant in Nature
7 1.5 Lesson 3: Disordered Proteins Are Globally Heterogeneous
9 1.6 Lesson 4: Hydrodynamic Dimensions of Natively Unfolded Proteins Are Charge Dependent
14 1.7 Lesson 5: Polymer Physics Explains Hydrodynamic Behavior of Disordered Proteins
16 1.8 Lesson 6: Natively Unfolded Proteins Are Pliable and Very Sensitive to Their Environment
18 1.9 Lesson 7: When Bound
Natively Unfolded Proteins Can Gain Unusual Structures
20 1.10 Lesson 8: IDPs Can Form Disordered or Fuzzy Complexes
25 1.11 Lesson 9: Intrinsic Disorder Is Crucial for Recognition
Regulation
and Signaling
25 1.12 Lesson 10: Protein Posttranslational Modifi cations Occur at Disordered Regions
28 1.13 Lesson 11: Disordered Regions Are Primary Targets for AS
30 1.14 Lesson 12: Disordered Proteins Are Tightly Regulated in the Living Cells
31 1.15 Lesson 13: Natively Unfolded Proteins Are Frequently Associated with Human Diseases
33 1.16 Lesson 14: Natively Unfolded Proteins Are Attractive Drug Targets
35 1.17 Lesson 15: Bright Future of Fuzzy Proteins
38 Acknowledgments
39 References
40 I CONFORMATIONAL ANALYSIS OF UNFOLDED STATES 55 2 Exploring the Energy Landscape of Small Peptides and Proteins by Molecular Dynamics Simulations 57 Gerhard Stock
Abhinav Jain
Laura Riccardi
and Phuong H. Nguyen 2.1 Introduction: Free Energy Landscapes and How to Construct Them
57 2.2 Dihedral Angle PCA Allows Us to Separate Internal and Global Motion
61 2.3 Dimensionality of the Free Energy Landscape
62 2.4 Characterization of the Free Energy Landscape: States
Barriers
and Transitions
65 2.5 Low-Dimensional Simulation of Biomolecular Dynamics to Catch Slow and Rare Processes
67 2.6 PCA by Parts: The Folding Pathways of Villin Headpiece
69 2.7 The Energy Landscape of Aggregating A²-Peptides
73 2.8 Concluding Remarks
74 Acknowledgments
75 References
75 3 Local Backbone Preferences and Nearest-Neighbor Effects in the Unfolded and Native States 79 Joe DeBartolo
Abhishek Jha
Karl F. Freed
and Tobin R. Sosnick 3.1 Introduction
79 3.2 Early Days: Random Coil--Theory and Experiment
80 3.3 Denatured Proteins as Self-Avoiding Random Coils
82 3.4 Modeling the Unfolded State
82 3.5 NN Effects in Protein Structure Prediction
86 3.6 Utilizing Folding Pathways for Structure Prediction
87 3.7 Native State Modeling
88 3.8 Secondary-Structure Propensities: Native Backbones in Unfolded Proteins
92 3.9 Conclusions
92 Acknowledgments
93 References
94 4 Short-Distance FRET Applied to the Polypeptide Chain 99 Maik H. Jacob and Werner M. Nau 4.1 A Short Timeline of Resonance Energy Transfer Applied to the Polypeptide Chain
99 4.2 A Short Theory of FRET Applied to the Polypeptide Chain
101 4.3 DBO and Dbo
105 4.4 Short-Distance FRET Applied to the Structured Polypeptide Chain
107 4.5 Short-Distance FRET to Monitor Chain-Structural Transitions upon Phosphorylation
116 4.6 Short-Distance FRET Applied to the Structureless Chain
120 4.7 The Future of Short-Distance FRET
125 Acknowledgments
125 Dedication
126 References
126 5 Solvation and Electrostatics as Determinants of Local Structural Order in Unfolded Peptides and Proteins 131 Franc Avbelj 5.1 Local Structural Order in Unfolded Peptides and Proteins
131 5.2 ESM
134 5.3 The ESM and Strand-Coil Transition Model
137 5.4 The ESM and Backbone Conformational Preferences
138 5.5 The Nearest-Neighbor Effect
141 5.6 The ESM and Cooperative Local Structures--Fluctuating ²-Strands
141 5.7 The ESM and ²-Sheet Preferences in Native Proteins--Significance of Unfolded State
144 5.8 The ESM and Secondary Chemical Shifts of Polypeptides
145 5.9 Role of Backbone Solvation in Determining Hydrogen Exchange Rates of Unfolded Polypeptides
148 5.10 Other Theoretical Models of Unfolded Polypeptides
148 Acknowledgments
149 References
149 6 Experimental and Computational Studies of Polyproline II Propensity 159 W. Austin Elam
Travis P. Schrank
and Vincent J. Hilser 6.1 Introduction
159 6.2 Experimental Measurement of PII Propensities
161 6.3 Computational Studies of Denatured State Conformational Propensities
168 6.4 A Steric Model Reveals Common PII Propensity of the Peptide Backbone
172 6.5 Correlation of PII Propensity to Amino Acid Properties
175 6.6 Summary
180 Acknowledgments
180 References
180 7 Mapping Conformational Dynamics in Unfolded Polypeptide Chains Using Short Model Peptides by NMR Spectroscopy 187 Daniel Mathieu
Karin Rybka
Jürgen Graf
and Harald Schwalbe 7.1 Introduction
187 7.2 General Aspects of NMR Spectroscopy
189 7.3 NMR Parameters and Their Measurement
191 7.4 Translating NMR Parameters to Structural Information
202 7.5 Conclusions
213 Acknowledgments
215 References
215 8 Secondary Structure and Dynamics of a Family of Disordered Proteins 221 Pranesh Narayanaswami and Gary W. Daughdrill 8.1 Introduction
221 8.2 Materials and Methods
223 8.3 Results and Discussion
226 Acknowledgments
235 References
235 II DISORDERED PEPTIDES AND MOLECULAR RECOGNITION 239 9 Binding Promiscuity of Unfolded Peptides 241 Christopher J. Oldfi eld
Bin Xue
A. Keith Dunker
and Vladimir N. Uversky 9.1 Protein-Protein Interaction Networks
241 9.2 Role of Intrinsic Disorder in PPI Networks
242 9.3 Transient Structural Elements in Protein-Based Recognition
243 9.4 Chameleons and Adaptors: Binding Promiscuity of Unfolded Peptides
256 9.5 Principles of Using the Unfolded Protein Regions for Binding
262 9.6 Conclusions
266 Acknowledgments
266 References
266 10 Intrinsic Flexibility of Nucleic Acid Chaperone Proteins from Pathogenic RNA Viruses 279 Roland Ivanyi-Nagy
Zuzanna Makowska
and Jean-Luc Darlix 10.1 Introduction
279 10.2 Retroviruses and Retroviral Nucleocapsid Proteins
280 10.3 Core Proteins in the Flaviviridae Family of Viruses
288 10.4 Coronavirus Nucleocapsid Protein
290 10.5 Hantavirus Nucleocapsid Protein
291 Acknowledgments
293 References
293 III AGGREGATION OF DISORDERED PEPTIDES 307 11 Self-Assembling Alanine-Rich Peptides of Biomedical and Biotechnological Relevance 309 Thomas J. Measey and Reinhard Schweitzer-Stenner 11.1 Biomolecular Self-Assembly
309 11.2 Misfolding and Human Disease
310 11.3 Exploitation of Peptide Self-Assembly for Biotechnological Applications
326 11.4 Concluding Remarks
340 Acknowledgments
340 References
340 12 Structural Elements Regulating Interactions in the Early Stages of Fibrillogenesis: A Human Calcitonin Model System 351 Rosa Maria Vitale
Giuseppina Andreotti
Pietro Amodeo
and Andrea Motta 12.1 Stating the Problem
351 12.2 Aggregation Models: The State of The Art
354 12.3 Human Calcitonin hCT as a Model System for Self-Assembly
356 12.4 The "Prefi brillar" State of hCT
358 12.5 How Many Molecules for the Critical Nucleus?
361 12.6 Modeling Prefi brillar Aggregates
366 12.7 hCT Helical Oligomers
366 12.8 The Role of Aromatic Residues in the Early Stages of Amyloid Formation
372 12.9 The Folding of hCT before Aggregation
373 12.10 Model Explains the Differences in Aggregation Properties between hCT and sCT
374 12.11 hCT Fibril Maturation
375 12.12 ±-Helix -->²-Sheet Conformational Transition and hCT Fibrillation
377 12.13 Concluding Remarks
378 Acknowledgments
378 References
379 13 Solution NMR Studies of A² Monomers and Oligomers 389 Chunyu Wang 13.1 Introduction
389 13.2 Overexpression and Purifi cation of Recombinant A²
390 13.3 A² Monomers
393 13.4 A² Oligomers and Monomer-Oligomer Interaction
403 13.5 Conclusion
406 References
406 14 Thermodynamic and Kinetic Models for Aggregation of Intrinsically Disordered Proteins 413 Scott L. Crick and Rohit V. Pappu 14.1 Introduction
413 14.2 Thermodynamics of Protein Aggregation--the Phase Diagram Approach
415 14.3 Thermodynamics of IDP Aggregation (Phase Separation)--MPM Description
420 14.4 Kinetics of Homogeneous Nucleation and Elongation Using MPMs
425 14.5 Concepts from Colloidal Science
427 14.6 Conclusions
433 Acknowledgments
433 References
434 15 Modifiers of Protein Aggregation--From Nonspecific to Specific Interactions 441 Michal Levy-Sakin
Roni Scherzer-Attali
and Ehud Gazit 15.1 Introduction
441 15.2 Nonspecific Modifi ers
442 15.3 Specific Modifiers
454 Acknowledgments
465 References
466 16 Computational Studies of Folding and Assembly of Amyloidogenic Proteins 479 J. Srinivasa Rao
Brigita Urbanc
and Luis Cruz 16.1 Introduction
479 16.2 Amyloids
480 16.3 Computer Simulations
485 16.4 Summary
514 References
515 INDEX 529