Biological Mass Spectrometry

512 Pages·1996·2.34 MB·English

by  A. L. Burlingame, Steven A. Carr

METHODS IN ENZYMOLOGY
EDITORS-IN-CHIEF
John N. Abelson Melvin I. Simon
DIVISION OF BIOLOGY
CALIFORNIA INSTITUTE OF TECHNOLOGY
PASADENA, CALIFORNIA
FOUNDING EDITORS
Sidney P. Colowick and Nathan O. Kaplan
Preface
Mass spectrometry deals with the formation, manipulation, and measurement
of charged substances in order to detect and identify them. Since its previous
overview was published in this series (McCloskey, 1990), the Nobel Prize in
Chemistry was awarded in 2002 to John B. Fenn and Koichi Tanaka for the
discovery of two new methods for producing charged biomacromolecules from
liquid and solid solution. These can be thought of as ways to isolate charged
molecules in the gas phase that are formed simply from ‘‘normal acid‐base
protonation‐deprotonation reactions’’ from volatile liquid buffers and solid
matrices. Over the past two decades these techniques, electrospray (ESI)
and matrix‐assisted laser desorption (MALDI), have provided the remarkable
window we needed to ‘‘see’’ into the machinery of cell biology and view its
true molecular complexity for the first time.
These ways of producing ions work efficiently for virtually all biomacromo-
lecules, so it is left to our scientific ingenuity to design ways to manipulate these
charged molecules to elicit information that reveals their molecular structural
nature. Hence, several generations of ion‐optical and energy deposition strate-
gies have emerged that make up the current tools of the trade—commercial
mass spectrometers. It should be noted that the design and discovery of better
strategies remains a vibrant, young pursuit.
Finally, advanced computational capabilities have evolved to record, pro-
cess, and manage mass spectral information and provide interfaces with DNA
and protein sequence repositories. The tools of bioinformatics are also being
adapted and refined to provide visualization into our existing knowledge of
biology.
But these developments represent just the beginning of positioning the kind
of ingredients that will be employed to gain an understanding of human biology.
This volume and its companion (Burlingame, 2005) are intended to describe
the astounding strides that have brought us to our current methodological
toolbox and also provide the foundation of knowledge indispensable to under-
standing the current practice of mass spectrometry, as well as to appreciate the
rapidly expanding and accelerating horizons in this field.
Thus, this work is focused at the forefront of proteins and their complexities,
including descriptions of the techniques and instrumentation being used, their
sequence and structural identification based on interpretation of their tandem
mass spectra, the strategies and issues in proteomics, studies of solution
ix
x preface
structures and interactions using isotope exchange, studies of non‐covalent
complexes with metal ions and ligands, and use of sub‐attomole isotopic bio‐
tracers using accelerator mass spectrometry. All of these contributions are
written by authorities who have made seminal contributions to their respective
topics.
These foundations provide insight into the forefront of the experimental and
technological platforms necessary to pursue a variety of major research themes
surrounding protein biology, including proteomics, protein‐protein interac-
tions, glycobiology, epi‐genetics, and systems biology.
I am indebted to all of my colleagues who have participated in this work, to
Candy Stoner for her assistance and talents during the preparation phase, and
to Raisa Talroze for the completion of both volumes. I would like to acknowl-
edge the NIH, National Center for Research Resources, for generous financial
support (Grant RR 01614).
A. L. BURLINGAME
References
Burlingame, A. L. (2005). ‘‘Mass Spectrometry: Modified Proteins and Glycoconjugates.’’
Meth. Enz. 405.
McCloskey, J. A. (1990). Mass spectrometry. Meth. Enz. 193, 960.
Table of Contents
CONTRIBUTORS TO VOLUME 402 . . . . . . . . . . . . . . . . . vii
PREFACE . . . . . . . . . . . . . . . . . . . . . . . . ix
VOLUMES IN SERIES . . . . . . . . . . . . . . . . . . . . . xi
Biological Mass Spectrometry
1. Mass Spectrometers for the Analysis of MICHAEL A. BALDWIN 3
Biomolecules
2. Hybrid Quadrupole/Time-of-Flight Mass WERNER ENS AND
Spectrometers for Analysis of Biomolecules KENNETH G. STANDING 49
3. Tandem Time-of-Flight Mass Spectrometry MARVIN L. VESTAL AND
JENNIFER M. CAMPBELL 79
4. Tandem Mass Spectrometry in Quadrupole ANNE H. PAYNE AND
Ion Trap and Ion Cyclotron Resonance GARY L. GLISH 109
Mass Spectrometers
5. Collision-Induced Dissociation (CID) of J. MITCHELL WELLS AND
Peptides and Proteins SCOTT A. MCLUCKEY 148
6. Peptide Sequencing by MALDI JOSEPH W. MORGAN,
193-nm Photodissociation TOF MS JUSTIN M. HETTICK, AND
DAVID H. RUSSELL 186
7. Peptide Sequence Analysis KATALIN F. MEDZIHRADSZKY 209
8. Proteomics JOHN T. STULTS AND
DAVID ARNOTT 245
9. Bioinformatic Methods to Exploit Mass ROBERT J. CHALKLEY,
Spectrometric Data for Proteomic KIRK C. HANSEN, AND
Applications MICHAEL A. BALDWIN 289
10. Protein Conformations, Interactions, and CLAUDIA S. MAIER AND
H/D Exchange MAX L. DEINZER 312
11. Ligand–Metal Ion Binding to Proteins: NOELLE POTIER,
Investigation by ESI Mass Spectrometry HE´ LE` NE ROGNIAUX,
GUILLAUME CHEVREUX, AND
ALAIN VAN DORSSELAER 361
v
vi table of contents
12. Site-Specific Hydrogen Exchange of Proteins: ZHONG-PING YAO,
Insights into the Structures of PAULA TITO, AND
Amyloidogenic Intermediates CAROL V. ROBINSON 389
13. Quantitating Isotopic Molecular Labels with JOHN S. VOGEL AND
Accelerator Mass Spectrometrty ADAM H. LOVE 402
14. Accelerator Mass Spectrometry for KAREN BROWN,
Biomedical Research KAREN H. DINGLEY, AND
KENNETH W. TURTELTAUB 423
AUTHOR INDEX . . . . . . . . . . . . . . . . . . . . . . 445
SUBJECT INDEX . . . . . . . . . . . . . . . . . . . . . . 471
Contributors to Volume 402
Article numbers are in parantheses following the name of Contributors.
Affiliations listed are current.
DAVID ARNOTT (8), Department of Protein KIRK C. HANSEN (9), School of Medicine,
Chemistry, Genetech, Inc., South San University of Colorado Health Sciences
Francisco, California Center, Aurora, Colorado
MICHAEL A. BALDWIN (1, 9), Mass Spectro- JUSTIN M. HETTICK (6), National Institute
metry Research Resource, Department for Occupational Safety and Health,
of Pharmaceutical Chemistry, Univer- Health Effects Laboratory Division,
sity of California, San Francisco, San Allergy and Clinical Immunology
Francisco, California Research, Washington, D.C.
KAREN BROWN* (14), Lawrence Liver- ADAM H. LOVE (13), Center for Accelera-
more National Laboratory, Livermore, tor Mass Spectrometry, Lawrence Liver-
California more National Laboratory, Livermore,
California
JENNIFER M. CAMPBELL (3), Applied Bio-
systems, Framingham, Massachusetts CLAUDIA S. MAIER (10), Department of
Chemistry, Oregon State University,
ROBERT J. CHALKLEY (9), Department of
Corvallis, Oregon
Pharmaceutical Chemistry, University
of California, San Francisco, San Fran- SCOTT A. MCLUCKEY (5), Department of
cisco, California Chemistry, Purdue University, West La-
fayette, Indiana
GUILLAUME CHEVREUX (11), Laboratoire
de Spe´ctrometrie de Masse Bio-Organi- KATALIN F. MEDZIHRADSZKY (7), De-
que (LSMBO), Strasbourg, France partment of Pharmaceutical Chemistry,
School of Pharmacy, University of Cali-
MAX L. DEINZER (10), Department of fornia, San Francisco, San Francisco,
Chemistry, Oregon State University, California; Proteomics Research Group,
Corvallis, Oregon Biological Research Center, Szeged,
Hungary
KAREN H. DINGLEY (14), Lawrence Liver-
more National Laboratory, Livermore, JOSEPH W. MORGAN (6), Department
California of Chemistry, Texas A&M University,
College Station, Texas
WERNER ENS (2), Department of Physics
and Astronomy, University of Manitoba, ANNE H. PAYNE (4), Department of Chem-
Winnipeg, Manitoba, Canada istry, University of North Carolina at
Chapel Hill, Chapel Hill, North Carolina
GARY L. GLISH (4), Department of Chem-
istry, University of North Carolina NOELLE POTIER (11), Laboratoire de Spe´c-
at Chapel Hill, Chapel Hill, North trometrie de Masse Bio-Organique,
Carolina Strasbourg, France
*Current address: Cancer Biomarkers and Prevention Group, The Biocentre, University
of Leicester, Leicester, United Kingdom.
vii
viii contributors to volume 402
CAROL V. ROBINSON (12), Department of KENNETH W. TURTELTAUB (14), Biology
Chemistry, University of Cambridge, and Biotechnology Research Program,
Cambridge, United Kingdom Lawrence Livermore National Labora-
tory, Livermore, California
HE´ LE` NE ROGNIAUX (11), INRA URPVI –
ALAIN VAN DORSSELAER (11), Laboratoire
Plate-forme de Spectrome´trie de Masse,
de Spe´ctrometrie de Masse Bio-Organi-
Nantes, France
que, Strasbourg, France
DAVID H. RUSSELL (6), Department
MARVIN L. VESTAL (3), Applied Bio-
of Chemistry, Texas A&M University,
systems, Framingham, Massachusetts
College Station, Texas
JOHN S. VOGEL (13), Center for Accelerator
KENNETH G. STANDING (2), Department
Mass Spectrometry, Lawrence Liver-
of Physics and Astronomy, University
more National Laboratory, Livermore,
of Manitoba, Winnipeg, Manitoba,
California
Canada
MITCHELL J. WELLS (5), Department
JOHN T. STULTS (8), Predicant Biosciences, of Chemistry, Purdue University, West
Inc., South San Francisco, California Lafayette, Indiana
PAULATITO (12), Department of Chemistry, ZHONG-PING YAO (12), Department of
University of Cambridge, Cambridge, Chemistry, University of Cambridge,
United Kingdom Cambridge, United Kingdom
[1] mass spectrometers for biomolecular analysis 3
[1] Mass Spectrometers for the Analysis
of Biomolecules
By MICHAEL A. BALDWIN
Abstract
Mass spectrometry (MS) has become a vital enabling technology in
the life sciences. This chapter summarizes the fundamental aspects of
MS, with reference to topics such as isotopic abundance and accurate mass
and resolution. A broad and comprehensive overview of the instrumenta-
tion, techniques, and methods required for the analysis of biomolecules
is presented. Emphasis is placed on describing the soft ionization meth-
ods and separation techniques employed in current state‐of‐the‐art mass
spectrometers.
As defined in a publication from the International Union of Pure and
Applied Chemistry (IUPAC), MS (or mass spectroscopy) is ‘‘the study of
systems by the formation of gaseous ions, with or without fragmentation,
which are then characterized by their mass‐to‐charge ratios and relative
abundances’’ (Todd, 1991). Since the publication of the last volume in
Methods in Enzymology reviewing MS of biomolecules (McCloskey,
1990), there has been a revolution in the field. Two promising novel soft
ionization methods emerging at that time were not generally available,
partly because both were largely incompatible with the typical commercial
sector mass spectrometers that were in widespread use. Although the
particle bombardment/desorption techniques of plasma desorption MS
(PDMS), fast atom bombardment (FAB), and liquid secondary ion MS
(LSIMS), invented a decade earlier, had been making valuable contribu-
tions to the analysis of peptides, oligosaccharides, and other polar and
involatile compounds, they were largely limited to the picomole range
and thus lacked the sensitivity needed to tackle the most challenging
problems. During that period when analysis of intact biological molecules
such as small proteins first became possible, much research was focused on
attempts to ionize ever larger molecules, many of which were standards
purchased from commercial suppliers. With hindsight, simply measuring
the molecular weight of a large molecule is often of limited utility, whereas
digesting it chemically or enzymatically to smaller moieties and measuring
the masses of even a subset of these can be very informative. Today, thanks
to the maturation of soft ionization methods and new developments
in mass analyzers optimized for these new ionization methods, MS is
METHODS IN ENZYMOLOGY, VOL. 402 0076-6879/05 $35.00
Copyright 2005, Elsevier Inc. All rights reserved. DOI: 10.1016/S0076-6879(05)02001-X
4 biological mass spectrometry [1]
established as a fundamental technology in the biological sciences in rou-
tine use in numerous laboratories worldwide. There is no doubt that it is
contributing to the solution of very many fundamental problems in biology
and medicine (Burlingame et al., 2000; Weston and Hood, 2004).
The selection of an optimal mass spectrometric method to tackle a
particular task is rarely a straightforward consideration. As an example,
MS is the enabling technology in the field of proteomics (deHoog andMann,
2004), which involves protein identification in very complexmixtures such as
cell lysates, tissues, or other biological samples, as well as the identification
of interacting partners (Deshaies et al., 2002), characterization of modifica-
tions, quantitation of expression levels, and studies of non‐covalent protein
complexes. In most cases, this involves an initial separation step, usually by
one‐dimensional (1D) or two‐dimensional (2D) gel electrophoresis, perhaps
labeling with an affinity‐tagged ligand, followed by proteolysis with a site‐
specific protease such as trypsin to generate peptides, possibly multiple
further separation/enrichment steps, then the mass spectrometric analysis
of the peptide mixtures. Some of the questions that arise in choosing a mass
spectrometer to carry out various aspects of these tasks are as follows:
What level of sensitivity is required?
How accurate must molecular weight measurements be, and is there
a limit to the accuracy that is required or even useful?
Will the determination of peptide molecular weight values be
sufficient or will sequence data be necessary, and if so, what are
the optimal techniques?
Is it better to separate the peptide mixtures before MS analysis, for
example, by high‐performance liquid chromatography (HPLC)‐MS,
or can sufficient information be obtained on unseparated mixtures?
If HPLC is not used, how will the selected method be affected by
impurities that may be difficult to remove?
What is the sample throughput, and is the technique amenable to
automation?
What will it cost?
Although such questions help to narrow the choices, ultimately there
will be a number of alternative solutions, each of which has individual
strengths and weaknesses.
Some Definitions and Principles
In addition to the 1991 IUPAC recommendations on nomenclature and
definitions (Todd, 1991), in the same year the Committee on Measure-
ments and Standards of the American Society for Mass Spectrometry also