Mass Spectrometry in Structural Biology and Biophysics Architecture, Dynamics, and Interaction of Biomolecules

by Kaltashov, Igor A.; Eyles, Stephen J.; Desiderio, Dominic M.; Nibbering, Nico M.

• ISBN13: 9780470937792
• ISBN10: 0470937793
• Edition: 2nd
• Format: Hardcover
• Copyright: 2012-04-03
• Publisher: Wiley

Summary

With its detailed and systematic coverage of the current state of biophysical mass spectrometry (MS), here is one of the first systematic presentations of the full experimental array of MS-based techniques used in biophysics, covering both fundamental and practical issues. The book presents a discussion of general biophysical concepts and a brief overview of traditional biophysical techniques before outlining the more advanced concepts of mass spectrometry. The new edition gives an up-to-date and expanded coverage of experimental methodologies and a clear look at MS-based methods for studying higher order structures and biopolymers. A must for researchers in the field of biophysics, structural biology, and protein chemistry.

Author Biography

IGOR A. KALTASHOV, PHD, is a Professor in the Department of Chemistry at the University of Massachusetts Amherst.

STEPHEN J. EYLES, PHD, is a Senior Lecturer in the Department of Biochemistry and Molecular Biology, and the Director of the Mass Spectrometry Center at the University of Massachusetts Amherst.

Table of Contents

Preface to the Second Edition	p. xi
Preface to the First Edition	p. xiii
General Overview of Basic Concepts in Molecular Biophysics	p. 1
Covalent Structure of Biopolymers	p. 1
Noncovalent Interactions and Higher Order Structure	p. 3
Electrostatic Interaction	p. 3
Hydrogen Bonding	p. 6
Steric Clashes and Allowed Conformations of the Peptide Backbone: Secondary Structure	p. 6
Solvent--Solute Interactions, Hydrophobic Effect, Side-Chain Packing, and Tertiary Structure	p. 7
Intermolecular Interactions and Association: Quaternary Structure	p. 9
The Protein Folding Problem	p. 9
What Is Protein Folding?	p. 9
Why Is Protein Folding So Important?	p. 10
What Is the Natively Folded Protein and How Do We Define a Protein Conformation?	p. 11
What Are Non-Native Protein Conformations?: Random Coils, Molten Globules, and Folding Intermediates	p. 12
Protein Folding Pathways	p. 13
Protein Energy Landscapes and the Folding Problem	p. 14
Protein Conformational Ensembles and Energy Landscapes: Enthalpic and Entropic Considerations	p. 14
Equilibrium and Kinetic Intermediates on the Energy Landscape	p. 16
Protein Dynamics and Function	p. 17
Limitations of the Structure--Function Paradigm	p. 17
Protein Dynamics under Native Conditions	p. 17
Is Well-Defined Structure Required for Functional Competence?	p. 18
Biomolecular Dynamics and Binding from The Energy Landscape Perspective	p. 19
Energy Landscapes Within a Broader Context of Nonlinear Dynamics: Information Flow and Fitness Landscapes	p. 21
Protein Higher Order Structure and Dynamics from A Biotechnology Perspective	p. 22
References	p. 22
Overview of Traditional Experimental Arsenal to Study Biomolecular Structure and Dynamics	p. 26
X-Ray Crystallography	p. 26
Fundamentals	p. 26
Crystal Structures at Atomic and Ultrahigh Resolution	p. 27
Crystal Structures of Membrane Proteins	p. 27
Protein Dynamics and X-Ray Diffraction	p. 28
Solution Scattering Techniques	p. 28
Static and Dynamic Light Scattering	p. 28
Small-Angle X-Ray Scattering	p. 29
Cryo-Electron Microscopy	p. 29
Neutron Scattering	p. 30
NMR Spectroscopy	p. 30
Heteronuclear NMR	p. 32
Hydrogen Exchange by NMR	p. 33
Other Spectroscopic Techniques	p. 34
Cumulative Measurements of Higher Order Structure: Circular Dichroism	p. 34
Vibrational Spectroscopy	p. 37
Fluorescence: Monitoring Specific Dynamic Events	p. 39
Other Biophysical Methods to Study Macromolecular Interactions and Dynamics	p. 41
Calorimetric Methods	p. 41
Analytical Ultracentrifugation	p. 43
Surface Plasmon Resonance	p. 45
Size Exclusion Chromatography (Gel Filtration)	p. 46
Electrophoresis	p. 47
Affinity Chromatography	p. 48
References	p. 48
Overview of Biological Mass Spectrometry	p. 52
Basic Principles of Mass Spectrometry	p. 52
Stable Isotopes and Isotopic Distributions	p. 53
Macromolecular Mass: Terms and Definitions	p. 57
Methods of Producing Biomolecular Ions	p. 57
Macromolecular Ion Desorption Techniques: General Considerations	p. 57
Electrospray Ionization	p. 58
Matrix Assisted Laser Desorption Ionization (MALDI)	p. 60
Mass Analysis	p. 63
General Considerations: m/z Range and Mass Discrimination, Mass Resolution, Duty Cycle, and Data Acquisition Rate	p. 63
Mass Spectrometry Combined with Separation Methods	p. 64
Tandem Mass Spectrometry	p. 65
Basic Principles of Tandem Mass Spectrometry	p. 65
Collision-Induced Dissociation: Collision Energy, Ion Activation Rate, and Dissociation of Large Biomolecular Ions	p. 66
Surface- and Photoradiation-Induced Dissociation	p. 68
Electron-Based Ion Fragmentation Techniques: Electron Capture Dissociation and Electron Transfer Dissociation	p. 71
Ion-Molecule Reactions in the Gas Phase: Internal Rearrangement and Charge Transfer	p. 71
Brief Overview of Common Mass Analyzers	p. 72
Mass Analyzer As an Ion Dispersion Device: Magnetic Sector Mass Spectrometry	p. 72
Temporal Ion Dispersion: Time-of-Flight Mass Spectrometer	p. 73
Mass Analyzer As an Ion Filter	p. 75
Mass Analyzer As an Ion-Storing Device: The Quadrupole (Paul) Ion Trap and Linear Ion Trap	p. 76
Mass Analyzer As an Ion Storing Device: FT ICR MS	p. 78
Mass Analyzer as An Ion Storing Device: Orbitrap MS	p. 80
Ion Mobility Analyzers	p. 81
Hybrid Mass Spectrometers	p. 82
References	p. 82
Mass Spectrometry Based Approaches to Study Biomolecular Higher Order Structure	p. 89
Direct Methods of Structure Characterization: Native Electrospray Ionization Mass Spectrometry	p. 89
Preservation of Noncovalent Complexes in the Gas Phase: Stoichiometry of Biomolecular Assemblies	p. 89
Utilization of Ion Chemistry in the Gas Phase to Aid Interpretation of ESI MS Data	p. 91
Dissociation of Noncovalent Complexes in the Gas Phase: Can It Lead to Wrong Conclusions?	p. 93
Evaluation of Macromolecular Shape in Solution: The Extent of Multiple Charging in ESI MS	p. 94
Macromolecular Shape in the Gas Phase: Ion Mobility--Mass Spectrometry	p. 97
How Relevant Are Native ESI MS Measurements? Restrictions on Solvent Composition in ESI	p. 98
Noncovalent Complexes by MALDI MS	p. 98
Chemical Cross-Linking for Characterization of Biomolecular Topography	p. 99
Mono- and Bifunctional Cross-Linking Reagents	p. 99
Chemical Cross-Linkers with Fixed Arm-Length: Molecular Rulers or Tape Measures?	p. 100
Mass Spectrometry Analysis of Chemical Cross-Linking Reaction Products	p. 102
Intrinsic Cross-Linkers: Methods to Determine Disulfide Connectivity Patterns in Proteins	p. 108
Other Intrinsic Cross-Linkers: Oxidative Cross-Linking of Tyrosine Side Chains	p. 109
Mapping Solvent-Accessible Areas with Chemical Labeling and Footprinting Methods	p. 110
Selective Chemical Labeling	p. 110
Nonspecific Chemical Labeling	p. 115
Hydrogen Exchange	p. 116
Hydrogen Exchange in Peptides and Proteins: General Considerations	p. 116
Probing Exchange Patterns with HDX MS at the Local Level	p. 116
References	p. 119
Mass Spectrometry Based Approaches to Study Biomolecular Dynamics: Equilibrium Intermediates	p. 127
Direct Methods of Monitoring Equilibrium Intermediates: Protein Ion Charge-State Distributions in ESI MS	p. 127
Protein Conformation as a Determinant of the Extent of Multiple Charging in ESI MS	p. 127
Detection and Characterization of Large-Scale Conformational Transitions by Monitoring Protein Ion Charge-State Distributions in ESI MS	p. 128
Detection of Small-Scale Conformational Transitions by Monitoring Protein Ion Charge-State Distributions	p. 130
Pitfalls and Limitations of Protein Ion Charge-State Distribution Analysis	p. 133
Chemical Labeling and Trapping Equilibrium States in Unfolding Experiments	p. 135
Characterization of the Solvent-Exposed Surfaces with Chemical Labeling	p. 135
Exploiting Intrinsic Protein Reactivity: Disulfide Scrambling and Protein Misfolding	p. 136
Structure and Dynamics of Intermediate Equilibrium States by Hydrogen Exchange	p. 137
Protein Dynamics and Hydrogen Exchange	p. 137
Global Exchange Kinetics in the Presence of Non-Native States: EX1, EX2, and EXX Exchange Regimes in a Simplified Two-State Model System	p. 138
A More Realistic Two-State Model System: Effect of Local Fluctuations on the Global Exchange Pattern Under EX2 Conditions	p. 141
Effects of Local Fluctuations on the Global Exchange Pattern Under EX1 and Mixed (EXX) Conditions	p. 143
Exchange in Multistate Protein Systems: Superposition of EX1 and EX2 Processes and Mixed-Exchange Kinetics	p. 144
Measurements of Local Patterns of Hydrogen Exchange in the Presence of Non-Native States	p. 146
Bottom-Up Approaches to Probing the Local Structure of Intermediate States	p. 146
Top-Down Approaches to Probing the Local Structure of Intermediate States	p. 150
Further Modifications and Improvements of HDX MS in Conformationally Heterogeneous Systems	p. 153
References	p. 153
Kinetic Studies By Mass Spectrometry	p. 160
Kinetics of Protein Folding	p. 160
Stopped-Flow Measurement of Kinetics	p. 160
Kinetic Measurements with Hydrogen Exchange	p. 162
Kinetics by Mass Spectrometry	p. 163
Pulse Labeling Mass Spectrometry	p. 163
Continuous-Flow Mass Spectrometry	p. 168
Stopped-Flow Mass Spectrometry	p. 169
Kinetics of Disulfide Formation During Folding	p. 171
Irreversible Covalent Labeling As a Probe of Protein Kinetics	p. 172
Kinetics of Protein Assembly	p. 174
Kinetics of Enzyme Catalysis	p. 178
References	p. 181
Protein Interactions: A Closer Look at the Structure--Dynamics--Function Triad	p. 186
Direct Methods of Monitoring Protein Interactions with Their Physiological Partners in Solution by ESI MS: From Small Ligands to Other Biopolymers	p. 186
Assessment of Binding Affinity with Direct ESI MS Approaches	p. 189
Indirect Characterization of Non-covalent Interactions Under Physiological and Near-Physiological Conditions	p. 190
Assessment of Ligand Binding by Monitoring Dynamics of âÇ£NativeâÇ  Proteins with Hydrogen--Deuterium Exchange (HDX MS)	p. 190
PLIMSTEX and Related Techniques: Binding Assessment by Monitoring Conformational Changes with HDX MS in Titration Experiments	p. 192
Binding Revealed by Changes in Ligand Mobility	p. 194
Indirect Characterization of Noncovalent Interactions Under Partially Denaturing Conditions	p. 194
Ligand-Induced Protein Stabilization Under Mildly Denaturing Conditions: Effect of Ligand Binding on Charge-State Distributions of Protein Ions	p. 195
SUPREX: Utilizing HDX Under Denaturing Conditions to Discern Protein--Ligand Binding Parameters	p. 196
Understanding Protein Action: Mechanistic Insights from the Analysis of Structure and Dynamics under Native Conditions	p. 198
Dynamics at the Catalytic Site and Beyond: Understanding Enzyme Mechanism	p. 198
Allosteric Effects Probed by HDX MS	p. 201
Going Full Circle with MS: Native ESI MS Reveals Structural Changes Predicted by HDX MS Measurements	p. 201
Understanding Protein Action: Mechanistic Insights from the Analysis of Structure and Dynamics under Non-Native (Partially Denaturing) Conditions	p. 203
References	p. 206
Other Biopolymers and Synthetic Polymers of Biological Interest	p. 212
Nucleic Acids	p. 212
Characterization of the Covalent Structure of Nucleic Acids	p. 212
DNA Higher Order Structure and Interactions with Physiological Partners and Therapeutics	p. 215
Higher Order Structure and Dynamics of RNA	p. 219
Oligosaccharides	p. 223
Covalent Structure of Oligosaccharides	p. 225
Higher Order Structure of Oligosaccharides and Interactions with their Physiological Partners	p. 226
Synthetic Polymers and their Conjugates with Biomolecules	p. 226
Covalent Structure of Polymers and Polymer--Protein Conjugates	p. 229
Higher Order Structure of Polymers and Polymer--Protein Conjugates	p. 232
References	p. 233
Mass Spectrometry on the Frontiers of Molecular Biophysics and Structural Biology: Perspectives and Challenges	p. 239
Mass Spectrometry and the Unique Challenges of Membrane Proteins	p. 239
Analysis of Membrane Proteins in Organic Solvents	p. 240
Analysis of Membrane Proteins Using Detergents	p. 241
Analysis of Membrane Proteins Utilizing Other Membrane Mimics	p. 244
Analysis of Membrane Proteins in Their Native Environment	p. 249
The Protein Aggregation Problem	p. 249
The Importance and Challenges of Protein Aggregation	p. 249
Direct Monitoring of Protein Aggregation and Amyloidosis with Mass Spectrometry	p. 250
Structure of Protein Aggregates, Amyloids, and Pre-Amyloid States	p. 253
The Many Faces of Complexity: Mass Spectrometry and the Problem of Structural Heterogeneity	p. 258
How Large Is âÇ£Too LargeâÇ ? Mass Spectrometry in Characterization of Ordered Macromolecular Assemblies	p. 263
Proteasomes	p. 264
Ribosomes	p. 264
Molecular Chaperones	p. 267
Complexity of Macromolecular Interactions In Vivo and Emerging Mass Spectrometry Based Methods to Probe Structure and Dynamics of Biomolecules in Their Native Environment	p. 269
Macromolecular Crowding Effect	p. 269
Macromolecular Properties In Vitro and In Vivo	p. 270
âÇ£LiveâÇ  Macromolecules: Equilibrium Systems or Dissipative Structures?	p. 271
References	p. 272
Appendix: Physics of Electrospray	p. 279
Index	p. 285
Table of Contents provided by Publisher. All Rights Reserved.