Protein Mass Spectrometry (eBook)

Julian Whitelegge (Herausgeber)

eBook Download: EPUB

2008 | 1. Auflage
552 Seiten
Elsevier Science (Verlag)
978-0-08-093203-3 (ISBN)

Infos

This book is designed to be a central text for young graduate students interested in mass spectrometry as it relates to study of protein structure and function as well as proteomics.
It is a definite must have work for:
- libraries at academic institutions with Master and Graduate programs in Biochemistry, Molecular Biology, Structural Biology and Proteomics,
- individual laboratories with interests covering these areas, and
- libraries and individual laboratories in the pharmaceutical and biotechnology industries.

. serves as an essential reference to those working in the field
. incorporates the contributions of prominent experts
. features comprehensive coverage and a logical structure

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This book is designed to be a central text for young graduate students interested in mass spectrometry as it relates to the study of protein structure and function as well as proteomics. It is a definite must-have work for:- libraries at academic institutions with Master and Graduate programs in biochemistry, molecular biology, structural biology and proteomics- individual laboratories with interests covering these areas - libraries and individual laboratories in the pharmaceutical and biotechnology industries.*Serves as an essential reference to those working in the field*Incorporates the contributions of prominent experts *Features comprehensive coverage and a logical structure

Inhalt

Front cover 1
Copyright page 3
Comprehensive Analytical Chemistry: Protein Mass Spectrometry 6
Contents 8
Contributors to Volume 52 14
Volumes in the series 20
Foreword 24
Protein mass spectrometry: A personal historical view 24
References 27
Preface 30
Series Editor's Preface 32
Chapter 1. An Introduction to the Basic Principles and Concepts of Mass Spectrometry 34
1. Opening Remarks 35
2. The Instrument 37
3. Vacuum Systems 37
4. Definitions 38
5. Resolution 39
6. Mass Accuracy 41
7. Isotopes 42
8. Reconciling Theoretical and Measured Masses 44
9. Charge State Assignment 44
10. The Need for Chromatography 45
11. The Myth of Defining Elemental Compositions 46
12. Desorption Ionization: Laser Desorption 47
13. Spray Ionization: Electrospray Ionization 49
14. Mass Analyzers 52
15. Time-of-Flight Mass Spectrometers 53
16. Linear Quadrupole Mass Filters 55
17. Quadrupole Ion Traps 56
18. Linear Ion Traps 59
19. Ion Cyclotron Cells and Fourier Transform Mass Spectrometry 60
20. The Orbitrap 62
21. Detectors 63
22. Electron Multipliers 64
23. Conversion Dynodes or High-Energy Dynodes 65
24. Quantification 65
25. Structural Elucidation by Mass Spectrometry 67
26. Gas Phase Ion Stabilities and Energetics of the Collisionally-Activated Dissociation Process 68
27. Collision-Induced Dissociation 69
28. Electron Capture Dissociation 71
29. Electron Transfer Dissociation 73
30. Scan Modes in Tandem Mass Spectrometry 73
31.Conclusions 76
Acknowledgements 77
References 77
Chapter 2. Characterization of Protein Higher Order Structure and Dynamics with ESI MS 80
1. Introduction 80
2. Charge-State Distributions of Protein Ions in ESI MS and Large-Scale Conformational Dynamics of Single Polypeptide Chains 81
3. Conformational Dynamics in Multi-Component Systems: Assembly of Hemoglobin Tetramers 84
4. Charge-State Distribution and the Estimation of the Solvent-Exposed Surface Areas of Proteins 88
5. Limitations of the Use of Charge-State Distributions for Determining Protein Conformational Heterogeneity 91
6. Future Outlook 92
Acknowledgements 93
References 94
Chapter 3. Noncovalent Protein Interactions 96
1. Introduction 96
2. Instrumentation and Technical Development 97
3. Protein Misfolding and Aggregation 100
4. Ligand-Receptor Interactions 107
5. Heterogeneous Complexes: TRAP 109
6. Subunit Exchange of Transthyretin 111
7. Future Directions 111
8. Conclusions 112
Acknowledgments 112
References 112
Chapter 4. Protein Analysis with Hydrogen—Deuterium Exchange Mass Spectrometry 116
1. Introduction 116
2. Experimental Protocol 121
3. Illustrative Examples 129
4. Conclusions 133
Acknowledgements 134
References 134
Chapter 5. Biochemical Reaction Kinetics Studied by Time-Resolved Electrospray Ionization Mass Spectrometry 136
1. Introduction 136
2. Time-Resolved ESI-MS 138
3. Selected Applications 142
4. Conclusions and Outlook 153
Acknowledgements 154
References 154
Chapter 6. Thermodynamic Analysis of Protein Folding and Ligand Binding by SUPREX 160
1. Introduction 160
2. The SUPREX Protocol 161
3. Evaluation of Thermodynamic Parameters 164
4. Quantitative Analysis of Ligand Binding 169
5. Unique Applications 174
6. Conclusion 179
References 179
Chapter 7. Microsecond Time-Scale Hydroxyl Radical Profiling of Solvent-Accessible Protein Residues 184
1. Introduction 184
2. Reagents for Surface Mapping 186
3. Fast Photochemical oxidation of Proteins (FPOP) 196
Acknowledgement 205
References 205
Chapter 8. Intact Protein Mass Measurements and Top-Down Mass Spectrometry: Application to Integral Membrane Proteins 212
1. Introduction 212
2. Intact Protein Mass Measurements 213
3. Ionization 221
References 227
Chapter 9. Probing the Structure and Function of Integral Membrane Proteins by Mass Spectrometry 230
1. Introduction 230
2. Technical Aspects of Mass Spectrometry of Integral Membrane Proteins 231
3. MS of Integral Membrane Proteins Provides Insight into Structure, Function and Mechanism 232
4. Conclusions 242
Acknowledgements 242
References 242
Chapter 10. Bottom-Up Mass Spectrometry Analysis of Integral Membrane Protein Structure and Topology 246
1. Introduction 247
2. IMP Structure and Characterization 247
3. Mass Spectrometry Instrumentation 249
4. General Considerations for Sample Preparation 251
5. Localizing Glycosylation Sites 253
6. Limited Proteolysis 255
7. Residue-Specific Chemical Modification 259
8. Photoaffinity Labeling of Binding-Site Residues 263
9. Cross-Linking 266
10. HsolD Exchange 267
11. Summary and Future Directions 269
Abbreviations 271
Acknowledgement 272
References 272
Chapter 11. Covalent Trapping of Protein Interactions in Complex Systems 278
1. Introduction 278
2. Protein Crosslinking 280
3. Interactome Methods 284
4. Interface and Topology Mapping 292
5. Future Directions 299
Abbreviations 301
Acknowledgements 301
References 301
Chapter 12. Phosphoproteomics 308
1. Introduction to Phosphoproteomics 308
2. Strategies for Enrichment of Phosphorylated Peptides 310
3. Mass Spectrometric Analysis of Phosphorylated Peptides 315
4. Quantitative Phosphoproteomics 318
5. Factors Affecting Phosphoproteomics 323
6. Conclusion 325
Acknowledgments 326
References 326
Chapter 13. Analysis of Protein-Tyrosine Phosphorylation by Mass Spectrometry 330
1. Introduction 330
2. Enrichment 332
3. Qualitative Analysis 334
4. Quantitative Analysis 338
5. Future Directions 342
6. Conclusions 343
Abbreviations 343
Acknowledgement 344
References 344
Chapter 14. Protein Histidine Phosphorylation 348
1. Introduction 349
2. Chemistry of Phosphohistidine 350
3. Protein Histidine Phosphorylation 351
4. Detection of Histidine Phosphorylation 364
5. Future Directions 372
6. Conclusion 379
Acknowledgements 379
References 379
Chapter 15. O-GlcNAc Proteomics: Mass Spectrometric Analysis of O-GlcNAc Modifications on Proteins 386
1. Introduction 387
2. Challenges to Mapping Sites of O-GlcNAc Modification 391
3. Early Efforts in O-GlcNAc Site-Mapping 393
4. Enzymatic Tagging of O-GlcNAc to Facilitate Enrichment and Identification of Modification Sites 394
5. Chemoenzymatic Approaches in O-GlcNAc Proteomics 395
6. Beta-EliminationsolMichael Addition Strategies for O-GlcNAcylation Site-Mapping 396
7. Direct Enrichment of Native O-GlcNAc Modified Proteins with WGA Lectin Weak Affinity Chromatography (LWAC) 398
8. Ion Trap MS2/MS3 for O-GlcNAc Modified Peptide Identification 399
9. Electron Capture Dissociation (ECD) for O-GlcNAc Site-Mapping 399
10. Interpretation of O-GlcNAcylated Peptide Mass Spectrometry 401
11. Conclusions 402
References 403
Chapter 16. Analysis of Deamidation in Proteins 408
1. What is Deamidationquest 409
2. How Does Deamidation Occurquest 410
3. Biological Significance of Deamidation 413
4. Non-MS Based Methods for Studying Deamidation 418
5. Mass Spectrometry Based Methods for Studying Deamidation 423
6. Quantitation of Deamidation and Its Products 430
7. Isotopic Labeling Methods 432
8. Summary 434
References 435
Chapter 17. Mass Spectrometry-Driven Approaches to Quantitative Proteomics and Beyond 444
1. Why to Use Mass Spectrometry in Quantitative Proteomics 444
2. MS-Based Approaches to Quantitative Proteomics 446
3. Applications in Functional Proteomics 459
4. How to Obtain Meaningful Data in MS-Based Quantitative Proteomics 470
5. Perspectives 472
References 472
Chapter 18. Multiplexed Quantitative Proteomics Using Mass Spectrometry 482
1. Introduction 482
2. Isobaric N-Terminal Peptide Tagging 485
3. Mass Spectrometry 490
4. Quantitative Applications Using Isobaric Tagging 494
References 499
Chapter 19. Large-Scale Subcellular Localization of Proteins by Protein Correlation Profiling 500
1. Introduction 500
2. Peptide Correlation Profiling 501
3. Other Quantitative Methods 506
4. Software for PCP 507
5. Hardware Requirements for PCP 508
6. The Future for PCP and Organelle Proteomics 508
Acknowledgements 509
References 509
Chapter 20. Metabolic Labeling Approaches for the Relative Quantification of Proteins 512
1. Introduction 513
2. Selected Metabolic Labeling Strategies 516
3. Practical Experimental Considerations 520
4. Comparison of Full versus Partial Labeling 531
5. Future Directions 540
References 542
Subject Index 548
Colour Plate Section 552

Textauszug

Foreword

Peter Roepstorff

Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark

Protein mass spectrometry: A personal historical view

In the early part of the 1990s the use of mass spectrometry for protein studies exploded due to the start of the proteomics era. Many young scientists in the field believe that protein mass spectrometry started at that time. This is not true. The first attempts to analyze peptides and proteins date back to the mid-1960s. A landmark publication for me personally was a paper by Mickey Barber and a number of French scientists in which they described the structure determination of a heavily and heterogeneously modified peptidolipid called Fortuitine with a molecular weight of 1,359 using electron impact (EI) mass spectrometry [1]. At that time all mass spectrometric analysis required volatile samples, i.e., samples which could be brought at the gas phase without thermal destruction by heating the sample. Fortuitine was a very fortuitous sample because it was N- and C-terminally blocked and in addition a number of the amide nitrogen atoms were methylated, all making the molecule more volatile. EI-ionization supplied sufficient energy to the molecular ion to cause fragmentation along the peptide backbone. The mass accuracy in the double focusing AEI MS9 electrostatic/magnetic sector instrument was so high that the mass of the molecular ions as well as the fragment ions could be determined with a mass accuracy of a few ppm. A few other groups worldwide were also trying to analyze peptides by mass spectrometry. Among the most prominent was Klaus Biemann at MIT, who combined the need for separation and mass spectrometry by producing derivatives of small peptides which were amenable for GCMS. He also developed computer programs to interpret the data. In a paper from 1966 [2] he has the following statement in a discussion: “In view of the small amount of material required (microgram quantities) and of the extreme speed (1–3 min of computer time) with which this objective and exhaustive interpretation is achieved, this approach shows considerable promise for the routine determination of the amino acid sequence of small peptides obtained upon partial hydrolysis of the oligopeptides resulting from enzymatic cleavage of large polypeptides. It should also be useful in synthetic work since the principle is independent of the end groups and additional protecting groups, the mass of which can be read in with the data”. This almost prophetical statement was really foreseeing the future of mass spectrometry in protein studies.

In the late 1960s and early1970s a number of groups including my own took up peptide mass spectrometry. We were still limited by the need of producing volatile derivatives. Two main lines were followed, the use of permethylated peptides developed by Das et al. [3] and further improved by Thomas et al. [4] using direct inlet probes, and the reduced and trimethyl silylated derivatives introduced by Biemann using separation and introduction of the samples by GCMS. At that time it gradually became clear that post-translational protein modifications were frequent and that mass spectrometry would be an important analytical method to identify and determine the nature and positions of these. My personal breakthrough, which changed the attitude of many of my colleagues from considering the combination of mass spectrometry and protein chemistry as a utopia to be potentially valuable for protein studies, was the discovery of γ-carboxy-glutamic acid residues in the blood clotting factors [5,6]. A number of other modifications such as methylations, acetylations and hydroxylations were also discovered by mass spectrometry in that period. Unfortunately, we could not prepare volatile derivatives of glycosylated and phosphorylated peptides and consequently not see these frequent modifications with our mass spectrometers. Another focus of peptide mass spectrometry was protein sequencing. There we were in competition with the stepwise chemical Edman degradation and the automated peptide sequencer. Due to the need for derivatization when using mass spectrometry and the limited peptide size we could analyze, we could not catch up with the sequencer. Whenever we made a little progress, for example, the ability to analyze peptide mixtures and automatically interpret the resulting complex spectra [7], we were outperformed by improvements of the sequencer. In the 1970s two new ionization methods, chemical ionization (CI) and field desorption (FD), were invented. Both were tested for peptide analysis, e.g. [8,9]. CI resulted in more uniform fragment peak intensity than EI throughout the mass range of the spectra but did not eliminate the need for volatile derivatives. FD was more promising because it allowed analysis of underivatized peptides. However, the spectra were extremely difficult to obtain because the desorption took place in a very short time window and with the scanning instruments used at that time, it was real luck to be at the right position of the scan when the peptide ion was generated. Consequently none of these new ionization techniques resulted in a breakthrough for protein mass spectrometry. In the 1970s mass spectrometry was recognized all over as a tool for discovery of certain types of protein modifications and for sequencing of N-terminally blocked peptides which were not amenable for Edman degradation. However, most of the time it was a hard uphill walk and only few scientists believed in us.

In the beginning of the 1980s the situation changed to excitement. The main reason was the developments in the nucleic acid field resulting in cDNA sequencing making de novo sequencing on the protein level partially redundant, and the advent of new ionization methods that allowed mass spectrometric analysis of underivatized peptides and intact proteins. Already in 1974 a new ionization method, plasma desorption mass spectrometry (PDMS), based on desorption of the sample directly from the solid state by bombardment with high energy (100 MeV) ions was described by McFarlanes group at Texas A&M [10]. The method remained largely unrecognized by protein mass spectrometrists until Bo Sundqvist and collaborators at the Uppsala University demonstrated that it was possible to obtain mass spectra of intact proteins using PDMS, first insulin [11] and later for larger proteins [12,13]. They also developed the first commercially available plasma desorption mass spectrometer through the spin-off company BioIon. It was a fully automated instrument based on the almost forgotten time-of-flight principle. I was lucky to collaborate with the group in Uppsala and to get the first of these new instruments in my laboratory and thereby to participate in this exciting new development. Independently Mickey Barber (the one who analyzed Fortuitine in 1964) published another method, fast atom bombardment (FAB) [14], that allowed desorption of underivatized peptides from a glycerol matrix. The method was quickly demonstrated also to allow mass spectrometry of insulin [15,16] and some larger intact proteins. FAB could readily be installed on existing sector field mass spectrometers (including our own) and therefore quickly became available in many laboratories, whereas acceptance of PDMS was slower because it required new instrumentation and also, due to the 252Cf source, extensive safety precautions. In the coming period most of the principles now used in proteomics were established. Thus, characterization of proteins by peptide mass mapping using FAB-MS was suggested by Howard Morris [17] and soon also taken up by PDMS, the later allowing digestion of the proteins after recording their mass spectra directly on the nitrocellulose-covered target. Thus a combined top-down and bottom-up strategy could be performed on a single sample preparation. Although FAB and PD being soft ionization methods, sufficient energy was supplied to the formed ions to cause some fragmentation. This was investigated for both methods and the now widely used nomenclature for mass spectrometric peptide fragmentation suggested [18]. To generate more fragment ions collision induced dissociation (CID) was introduced in mass spectrometric peptide analysis using either triple quadrupole or the giant four sector instruments. The latter were extensively used by Klaus Biemann, e.g. [19]. They allowed high-resolution mass spectra to be recorded from parent as well as fragment ions and he succeeded in de novo sequencing of several small- to medium-sized proteins using such instruments. The now key element in proteomics, i.e., identification of proteins and peptides based on comparison of their mass with cDNA sequence information was also initiated in that period [20,21].

The scientists who in the 1980s investigated the possibility for mass spectrometry of involatile molecules were a rather small group dominated by physicists who tried to understand the desorption phenomenon but included a few chemists and biologists who wanted to apply the techniques. The group, including among many others Franz Hillenkamp, Ken Standing, Michael Karas, Brian Chait and Marvin Vestal, met at regular symposia, first the Ion Formation of Organic Solids (IFOS) meetings organized by A. Benninghoven and later the Desorption meetings. The atmosphere was enthusiastic with open exchange of information. By that time it became clear to us that the FAB and PD were limited in terms of the molecular size of the proteins to approximately 25 kDa and 35 kDa, respectively. Although the methods...

Produkt-Details

• Erscheint lt. Verlag: 9.10.2008
• Sprache: englisch
• Themenwelt: Informatik ► Weitere Themen ► Bioinformatik
• Themenwelt: Mathematik / Informatik ► Mathematik
• Themenwelt: Naturwissenschaften ► Biologie ► Biochemie
• Themenwelt: Naturwissenschaften ► Biologie ► Genetik / Molekularbiologie
• Themenwelt: Naturwissenschaften ► Chemie ► Analytische Chemie
• Themenwelt: Naturwissenschaften ► Chemie ► Technische Chemie
• Themenwelt: Naturwissenschaften ► Physik / Astronomie
• Themenwelt: Sozialwissenschaften ► Soziologie
• Themenwelt: Technik
• ISBN-10: 0-08-093203-7 / 0080932037
• ISBN-13: 978-0-08-093203-3 / 9780080932033