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Bio-nanoimaging
Protein Misfolding and Aggregation
1st Edition - November 5, 2013
Editors: Vladimir N Uversky, Yuri Lyubchenko
Hardback ISBN:9780123944313
9 7 8 - 0 - 1 2 - 3 9 4 4 3 1 - 3
eBook ISBN:9780123978219
9 7 8 - 0 - 1 2 - 3 9 7 8 2 1 - 9
Bio-Nanoimaging: Protein Misfolding & Aggregation provides a unique introduction to both novel and established nanoimaging techniques for visualization and characterization of… Read more
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Bio-Nanoimaging: Protein Misfolding & Aggregation provides a unique introduction to both novel and established nanoimaging techniques for visualization and characterization of misfolded and aggregated protein species. The book is divided into three sections covering:- Nanotechnology and nanoimaging technology, including cryoelectron microscopy of beta(2)-microglobulin, studying amyloidogensis by FRET; and scanning tunneling microscopy of protein deposits - Polymorphisms of protein misfolded and aggregated species, including fibrillar polymorphism, amyloid-like protofibrils, and insulin oligomers- Polymorphisms of misfolding and aggregation processes, including multiple pathways of lysozyme aggregation, misfolded intermediate of a PDZ domain, and micelle formation by human islet amyloid polypeptide
Protein misfolding and aggregation is a fast-growing frontier in molecular medicine and protein chemistry. Related disorders include cataracts, arthritis, cystic fibrosis, late-onset diabetes mellitus, and numerous neurodegenerative diseases like Alzheimer's and Parkinson's. Nanoimaging technology has proved crucial in understanding protein-misfolding pathologies and in potential drug design aimed at the inhibition or reversal of protein aggregation. Using these technologies, researchers can monitor the aggregation process, visualize protein aggregates and analyze their properties.
Provides practical examples of nanoimaging research from leading molecular biology, cell biology, protein chemistry, biotechnology, genetics, and pharmaceutical labs
Includes over 200 color images to illustrate the power of various nanoimaging technologies
Focuses on nanoimaging techniques applied to protein misfolding and aggregation in molecular medicine
Researchers and post-graduate students studying molecular medicine and molecular basis of disease, biotechnology, nanomedicine, pharmacology and drug discovery, molecular and cellular biology, biochemistry, biophysics, structural biology
Chapter 1. Molecular Mechanisms of Protein Misfolding
Abstract
Introduction
The Mechanism of Aggregation
Structures of Protein Aggregates
Protein Aggregation Pathways
Conclusions
References
Part I: Nanoimaging and Nanotechnology of Aggregating Proteins: A. In Vitro Approaches
Chapter 2. Amyloid Fibril Length Quantification by Atomic Force Microscopy
Abstract
Acknowledgments
Background
Acquiring Images for Length Quantification
Single-Particle Measurements of Individual Fibril Length
Distributions of Fibril Length
Prospects for Fibril Length Distribution Analysis
References
Chapter 3. Imaging Nucleation, Growth and Heterogeneity in Self-Assembled Amyloid Phases
Abstract
Acknowledgments
Introduction
Diversity in cross-β Assemblies
Particle Phases
Paracrystallization
Paracrystalline Polymorphism
Functional Energy Transfer
Closing Perspective
References
Chapter 4. Molecular-Level Insights into Amyloid Polymorphism from Solid-State Nuclear Magnetic Resonance
Abstract
Acknowledgments
Introduction
Self-Propagating Molecular-Level Polymorphism in Aβ1-40 Fibrils
Competition Between Parallel and Antiparallel β-Sheets in D23N-Aβ1-40 Fibrils
pH-Dependent Cross-β Motif in Aβ11-25 Fibrils
Polymorphism in Prion Fibrils
Future Directions
References
Chapter 5. Single-Molecule Imaging of Amyloid-β Protein (Aβ) of Alzheimer’s Disease: From Single-Molecule Structures to Aggregation Mechanisms and Membrane Interactions
Abstract
Introduction
Principles of High-Resolution Imaging by STM and AFM
Monomeric and Oligomeric Structures of Aβ Determined by STM and AFM
Mechanism of Aβ Fibrillogenesis Examined by AFM
Aβ Structure on Model Membranes Examined by High-Resolution AFM
Models of Aβ Structure Based on High-Resolution Imaging
References
Chapter 6. Nanomechanics of Neurotoxic Proteins: Insights at the Start of the Neurodegeneration Cascade
Abstract
Acknowledgments
Introduction
Intrinsically Disordered Proteins: Central Roles and Fatal Diseases
Amyloidogenic Neurodegenerative Diseases: A Subset of Conformational Diseases
Single-Molecule Analysis of Neurotoxic Proteins
Molecular Dynamics Simulations of Amyloidogenesis by Neurotoxic Proteins
Future Perspectives
References
Chapter 7. Reporters of Amyloid Structural Polymorphism
Abstract
Background and Rationale
Ligand-Binding Phenotype
Probes that Report their Conformation and Environment
Assessing Pathology Spread and Quantification
Applications and Implications of Polymorphism-Sensitive Reporters
References
Chapter 8. Conformation-Dependent Antibodies as Tools for Characterization of Amyloid Protein Aggregates
Abstract
Introduction
Amyloid Fibrils and Oligomers have Defined, Unique Tertiary Structures and Molecular Polymorphisms that are Recognized by Conformation-Specific Antibodies
Types of Conformation-Specific Antibodies Against Protein Aggregates
Sequence-Specific Antibodies
Sequence-Independent Antibodies
Conformation-Specific Antibodies as Probes for Studying Protein Structure and Changes in Conformation Underlying Protein Aggregation
Conformation-Specific Antibodies Recognize Polymorphism Within Amyloid Oligomers and Fibrils
Conformation-Specific Antibodies as Probes for Studying Protein-Folding Mechanisms
Therapeutic Applications of Conformation-Specific Antibodies in Neurodegenerative Diseases
Conclusions
References
Part II: Nanoimaging and Nanotechnology of Aggregating Proteins: B. In Vivo Approaches
Chapter 9. Analyzing Alzheimer’s Disease-Related Protein Deposition In Vivo By Multiphoton Laser Scanning Microscopy
Abstract
Protein Aggregation in Alzheimer’s Disease
In Vivo Multiphoton Imaging
Imaging Functional Changes Induced by AD-Related Pathology
Limitations of In Vivo Multiphoton Imaging
Conclusions
References
Chapter 10. Probing Amyloid Aggregation and Morphology In Situ by Multiparameter Imaging and Super-Resolution Fluorescence Microscopy
Abstract
Acknowledgments
Introduction
Multi-Parameter Microscopy of Protein Aggregation Kinetics
Super-Resolution Imaging of Amyloid Aggregation
Conclusion
References
Chapter 11. Imaging of Amyloid-β Aggregation Using a Novel Quantum dot Nanoprobe and its Advanced Applications
Abstract
Introduction of Amyloid-β Peptide Biology and Quantum dot Properties
Preparation of the Quantum dot Nanoprobe
In Vitro Imaging and Quantification of Aβ Aggregation
Imaging of Aβ Behaviors in Live Cell Cultures
High-Throughput Microscreening of Substances Inhibitory to Aβ Aggregation
Current Problems and Future Possibilities of this Imaging Technology
References
Chapter 12. Studying the Molecular Determinants of Protein Oligomerization in Neurodegenerative Disorders by Bimolecular Fluorescence Complementation
Abstract
Acknowledgments
Introduction
Neurodegenerative Disorders and Protein Misfolding
Protein Oligomerization, Aggregation and Toxicity
Protein Complementation Assays: History and Latest Developments
Advantages of BiFC Systems for Studying Protein Interactions
Protein Complementation Assays for the Study of Neurodegenerative Disorders
Methods
References
Chapter 13. Structure-Specific Intrinsic Fluorescence of Protein Amyloids Used to Study their Kinetics of Aggregation
Abstract
Acknowledgments
Introduction
Characterization of Oligomers Using Tryptophan and Tyrosine Fluorescence
Certain Protein Crystals and Aggregates Develop Intrinsic Fluorescence in the Visible Range
Intrinsic Fluorescence Arising from Disease-related Protein Amyloids During Aggregation
Does the Intrinsic Fluorescence of Protein Amyloids Provide Novel Insights into their Remarkable Stability?
Intrinsic Amyloid Fluorescence Informs on the Kinetics of Amyloid Formation and Mechanisms of Protein Misfolding Diseases
Conclusions
Future Work
References
Chapter 14. Real-Time Monitoring of Inclusion Formation in Living Zebrafish
Abstract
Introduction
Zebrafish as a Model Organism
Techniques for Generating Aggregation Models in Zebrafish
Time-Lapse In Vivo Imaging Techniques
Modeling Inclusion Formation in an HD Model in Zebrafish
In Vivo Imaging of Inclusion Formation in Zebrafish
Concluding Remarks and Outlook
References
Chapter 15. Scanning for Intensely Fluorescent Targets (SIFT) in the Study of Protein Aggregation at the Single-Particle Level
Abstract
The Role of Protein Aggregation in Neurodegeneration
Measuring protein aggregation: from fibril formation to single-particle analysis
The SIFT Method: Introduction and Technical Background
Methods of Analysis
Practical Applications
Pitfalls and Common Misconceptions
References
Part III: Polymorphism of Protein Misfolding and Aggregated Species
Chapter 16. The Molecular Basis For TGFBIp-Related Corneal Dystrophies
Abstract
Acknowledgments
Introduction
Challenges in Understanding the Role of TGFBIp in Corneal Dystrophies
Molecular Properties of TGFBIp: A Multidomain Protein with Four Homologous Domains
TGFBIp and Corneal Dystrophy
CD Mutations Induce Different TGFBIP Aggregation Mechanisms
CD and Changes in Proteolytic Processing of TGFBIp
TGFBIp Oligomerization
TGFBIp and Macromolecular Interactions
Aggregation Mechanism and Phenotypes
Future Treatment
References
Chapter 17. Aβ Fibril Polymorphism and Alzheimer’s Disease
Abstract
Acknowledgments
Alzheimer’s Disease: Relevance, Neuropathology and Etiology
Cellular Formation and Chemical Variability of Aβ Peptide
The Amyloid Hypothesis and the Putative Mechanism of Pathogenesis
General Topology and Polymorphism of Aβ Fibrils
Towards the Atomic Structures of Different Aβ Fibril Polymorphs
The Molecular Basis of Aβ Fibril Polymorphism
Biologic Relevance of Polymorphic Fibril Structures
References
Chapter 18. Structural Heterogeneity and Bioimaging of S100 Amyloid Assemblies
Abstract
Acknowledgments
Introduction
Structural Diversity of S100 Monomers and Multimers
S100 Oligomers, Aggregates and Amyloids
Bioimaging of S100 Amyloids by AFM and TEM
Conclusions
References
Chapter 19. Polymorphism of Tau Fibrils
Abstract
Introduction
Polymorphic Nature of Pathologic Tau Fibrils
Factors Affecting the Morphology of Tau Fibrils
A ‘Core’ Hypothesis for Generating Fibril Polymorphism
Perspectives
References
Chapter 20. Amyloid-Like Protofibrils with Different Physical Properties
Abstract
Acknowledgments
Introduction
Protofibril Polymorphism
Coexistence of Different Protofibril Populations
Mechanical Properties of Protofibrils
Concluding Remarks
References
Chapter 21. Insulin Oligomers: Detection, Characterization and Quantification Using Different Analytical Methods
Abstract
Introduction
Spectroscopy
Scattering Techniques
Microscopy
Separation Techniques
Indirect Measurements
Conclusions
References
Chapter 22. Imaging the Morphology and Structure of Apolipoprotein Amyloid Fibrils
Abstract
Introduction
ApoA-I
ApoE
ApoC-II
Structural Analysis of apoC-II Amyloid Fibrils
Summary
References
Chapter 23. Polymorphism of Amyloid Fibrils and their Complexes with Catalase
Abstract
Introduction
Catalase Interactions with Amyloid-β, Islet Amyloid Polypeptide and Prion Protein Fragments
Binding of Catalase to Aβ, IAPP and PrP Fibrils
The Shared Amyloid Catalase Recognition Sequence and Other Potential Amyloid Fibril Interactions
Use of Catalase Binding to Amyloid Fibrils in Drug Discovery
Conclusion
References
Chapter 24. On Possible Function and Toxicity of Multiple Oligomeric/Conformational States of a Globular Protein – Human Stefin B
Abstract
Acknowledgments
Introduction
Defining Intermediate States from which Amyloid Fibrils were Initiated
Kinetic Model and Morphologies of Amyloid Fibril Formation
Structural Data on Stefin Oligomers and the Role of Proline Isomerism
Selective Interaction of the Tetramer of Stefin B with Aβ
The Role of Copper
Membrane Binding and Pore Formation
Conclusions and Perspective
References
Chapter 25. Fibrillar Structures of Yeast Prion Sup35 In Vivo
Abstract
Introduction
Yeast Prion Sup35 as a Model Amyloid-Forming Protein in Cells
In Vitro Fibril Formation of Sup35
Structures of Sup35 Amyloids in Yeast Cells
Dynamic Properties of Sup35 Amyloids in Living Yeast Cells
Concluding Remarks
References
Chapter 26. Glycosaminoglycans and Fibrillar Polymorphism
Abstract
Acknowledgments
Introduction
Proteoglycan Components Responsible for Protein Binding and Fibril Enhancement
The Polymeric Nature of GAGs is Important for Inducing Mature Amyloid Fibrils
GAGs Affect Fibril Morphology in Different Ways
Specificity of GAG–Protein Interactions
GAGs can Induce Fibrils in Non-Amyloidogenic Proteins
GAGs can Accelerate Fibrillation by Binding Monomers or by Interacting with Oligomers
Future Perspectives and Challenges: the Importance of Molecular Insights
The Role of Dopamine in a Healthy Brain and in Parkinson’s Disease
α-Synuclein:DA Oligomers – Discovery and Properties
Shape and Structure of α-syn:DA Oligomers
How Does DA Link α-syn Molecules?
How Does DA Inhibit α-Synuclein Fibril Formation?
Biologic Significance of α-syn:DA Oligomers
References
Chapter 28. The Formation of Amyloid-Like Superstructures: On the Growth of Amyloid Spherulites
Abstract
Acknowledgments
Large-Scale Polymorphism in Protein Aggregation
Amyloid Spherulites: Hypotheses on the Structural Arrangement
Factors Affecting the Formation of Insulin Amyloid Spherulites
Conclusions and Perspectives
References
Chapter 29. Characterizing Nanoscale Morphologic and Mechanical Properties of α-Synuclein Amyloid Fibrils with Atomic Force Microscopy
Abstract
Introduction
aS Fibrils on Different Solid Surfaces
Preparation of Supported Lipid Bilayers on Mica
α-Synuclein Monomers on Supported Bilayers
α-Synuclein Fibrils on POPC-Supported Bilayers
Inferring the Mechanical Properties of Fibrils from Images
Wild-Type Fibrils on a POPC–POPG Supported Bilayer
Conclusions
Materials and Methods
References
Chapter 30. Polymorphism in Casein Protein Aggregation and Amyloid Fibril Formation
Abstract
Acknowledgments
Introduction to the Casein Proteins
Amorphous Aggregation Properties of Casein Proteins Under Native Conditions
Amyloid Fibril Formation by κ- and αs2-Casein Proteins
Modification and Inhibition of κ- and αs2-Casein Amyloid Fibril Formation by β- and αs1-Caseins
Potential Bio-Nanomaterial Applications of Casein Amyloid Fibrils
Conclusions
References
Chapter 31. Structural Basis for the Polymorphism of β-Lactoglobulin Amyloid-Like Fibrils
Abstract
Acknowledgments
Why β-Lactoglobulin?
Formation Mechanisms of Amyloid-Like Fibrils From β-Lactoglobulin
Polymorphism of β-Lactoglobulin Amyloids: Rod-Like, Worm-Like and Straight Fibrils
Molecular Structure of Amyloid Fibrils
Conclusions
References
Chapter 32. Fibrillation and Polymorphism of Human Serum Albumin
Abstract
Introduction
The Origin of Protein Misfolding
The Fibrillation Process of Human Serum Albumin
Conclusions and Outlook
References
Chapter 33. Formation of α-Helix-Based Twisted Ribbon-Like Fibrils from Ionic-Complementary Peptides
Abstract
Acknowledgments
Introduction
EMK8-II with Protected Terminus Forms Twisted Ribbon-Like Fibrils
Structural Characteristics of EMK8-II Fibrils
Assembly Dynamics of EMK8-II Fibrils
Cooperative Balance of Hydrophobicity and Ionic Interactions
The Assembly Mechanism of α-Helix-Based Fibrils
References
Chapter 34. Polymorphism, Metastable Species and Interconversion: The Many States of Glucagon Fibrils
Abstract
Acknowledgments
Introduction
The Basis of Fibril Polymorphism: Different Protofilament Packing and/or Different Protofilaments
How to Obtain Different Types of Glucagon Fibril: An Overview of the Current Literature
A Time-Resolved SAXS Study of the Effect of Shaking on Fibrillation and Fibril Structure: Different Degrees of Protofilament Association Under Quiescent and Shaking Conditions
Interconversion Between Fibril Morphologies: Metastable Fibril States Destabilized by Elevated Temperatures
Hydration and Packing Modulate Fibrillation and Fibril Stability
Inhibition of Glucagon Fibrillation by Modified Cyclodextrins
Perspectives: Stable or Unstable Fibrils in vivo?
References
Part IV: Polymorphism of Protein Misfolding and Aggregation Processes
Chapter 35. Multiple Pathways of Lysozyme Aggregation
Abstract
Introduction
Polymorphism of Amyloid Intermediates and Multiple Assembly Pathways
Characterizing Lysozyme Assembly Pathways and their Respective Intermediates with Atomic Force Microscopy
Physical Characterization of Transient Intermediates
Conclusions and Discussion
References
Chapter 36. Structure–Function Studies of Amyloid Pores in Alzheimer’s Disease as a Case Example of Neurodegenerative Diseases
Abstract
Acknowledgments
General Properties of Amyloids
Amyloids in Alzheimer’s Disease
Interaction of Peptides With the Cell Membrane
Pore Hypothesis
Structural and Functional Studies of Amyloid Pores
Alternative Mechanisms
References
Chapter 37. Nanoscale Optical Imaging of Protein Amyloids
Abstract
Acknowledgments
Introduction
Structural Biology of Amyloids
Nanoscale Biophysics of Amyloid Fibrils Using Super-Resolution Optical Imaging
Chapter 39. Role of Aberrant α-Synuclein–Membrane Interactions in Parkinson’s Disease
Abstract
Introduction
Evidence for Membrane-Induced α-Syn Self-Assembly
Conformations of α-Syn at the Membrane Surface
A Role for Aberrant α-Syn–Membrane Interactions in Neurotoxicity
Concluding Remarks
References
Chapter 40. ELOA – Equine Lysozyme Complexes with Oleic Acid: Structure and Cytotoxicity Studied by Bio-Imaging Techniques
Abstract
Acknowledgments
Introduction
HAMLET: Occurrence in Vivo and in Vitro
Structural Similarity of EL and α-LactalbuminS
The Production of HAMLET-type complexes
Protein Conformation in ELOA
ELOA Oligomeric Structure
ELOA Interaction With Lipid Bilayers
ELOA Cellular Toxicity
Conclusions
References
Chapter 41. Structure of a Misfolded Intermediate of a PDZ Domain
Abstract
Acknowledgments
Introduction
Results
Conclusions
References
Chapter 42. Intranuclear Amyloid – Local and Quantitative Analysis of Protein Fibrillation in the Cell Nucleus
Abstract
Acknowledgments
Disease-Associated Protein Fibrillation
Functional Amyloid
Characterization of nuclear protein fibrillation
Conclusions
References
Chapter 43. Conversion of α-Helical Proteins into an Alternative β-Amyloid Fibril Conformation
Abstract
Introduction to the Fibril Field
Transition of α-Helical Proteins into Amyloid-Like Fibrils
Polymorphism of Fibrillar Species Associated with α-Helical Proteins
Future Perspectives
References
Chapter 44. The Effect of Shear Flow on Amyloid Fibril Formation and Morphology
Abstract
Introduction
Shear Flow and Protein Misfolding
Effect of Shear Flow on Fibril Formation
Observed Structures: Impact of Flow on Fibril Structure and Mechanics
Conclusions
References
Subject Index
Name Index
No. of pages: 552
Language: English
Published: November 5, 2013
Imprint: Academic Press
Hardback ISBN: 9780123944313
eBook ISBN: 9780123978219
VU
Vladimir N Uversky
Vladimir N. Uversky is a Professor at the Department of Molecular Medicine, University of
South Florida, USA. He obtained B.S. and M.S. degrees in Physics from Leningrad State
University in Russia in 1986, then completed Ph.D. and Doctor of Sciences (D.Sc.) degrees
in Physics and Mathematics (field of study - Biophysics) at the Moscow Institute of Physics and Technology (1991) and the Institute Experimental and Theoretical Biophysics of the Russian Academy of Sciences (1998), respectively. In 1998, he moved to the University of California Santa Cruz to study protein folding, misfolding, protein conformation diseases, and protein intrinsic disorder phenomena. In 2004, he was invited to join the Indiana University School of Medicine to primary work on intrinsically disordered proteins, and since 2010 has been on faculty at the University of South Florida. He has authored over 850 scientific publications and edited several books and book series on protein structure.
Affiliations and expertise
Professor, Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, USA