Mass Spectrometry Methods for Studying Structure and Dynamics of Biological Macromolecules
Analytical ChemistryPublished 4 December 2013
Lars Konermann, Siavash Vahidi, Modupeola A. Sowole
Citations132
SJR quartileQ1
SJR score1.53
SNIP1.26
Generate an AI Snapshot to get a quick, structured summary of this paper.
Study Snapshot
ObjectiveStudy objective
MethodsResearch methodology
PopulationPopulation studied
Sample sizeSample sizes
OutcomesStudy outcomes here
ResultsStudy results comes here
LimitationsResearch study limitations comes here
A concise AI-generated summary of the paper will appear here once you click Generate AI Snapshot.
TL;DR
This paper presents a meta-analyses of proteolytic Digestion-LC/MS and ESI of the determinants of Binding Interactions of Protein−Protein Complexes and other types of Noncovalent Assemblies, and some of the techniques used for probing Gas Phase Structures.
Abstract
ADVERTISEMENT RETURN TO ISSUEPREVReviewNEXTMass Spectrometry Methods for Studying Structure and Dynamics of Biological MacromoleculesLars Konermann*, Siavash Vahidi, and Modupeola A. SowoleView Author Information Department of Chemistry, The University of Western Ontario, London, Ontario, N6A 5B7 Canada*E-mail: [email protected]. Phone: (519) 661-2111 ext. 86313.Cite this: Anal. Chem. 2014, 86, 1, 213–232Publication Date (Web):December 4, 2013Publication History Received3 December 2013Published online10 December 2013Published inissue 7 January 2014https://doi.org/10.1021/ac4039306Copyright © 2013 American Chemical SocietyRIGHTS & PERMISSIONSArticle Views5858Altmetric-Citations108LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit Read OnlinePDF (7 MB) Get e-AlertsSUBJECTS:Gases,Ions,Labeling,Nucleic acid structure,Peptides and proteins Get e-Alerts
Keywords
ChemistryBiochemistry, Genetics and Molecular Biology
Analytical ChemistryLaser desorption ionization of proteins with molecular masses exceeding 10,000 daltons
5,558 Citations1988Michael Karas, Franz Hillenkamp
In the following, the first results on ultraviolet laser desorption (UVLD) of bioorganic compounds in the mass range above 10000 daltons are reported.
Nature Reviews Molecular Cell BiologyIntrinsically unstructured proteins and their functions
3,878 Citations2005H. Jane Dyson, Peter E. Wright
Many gene sequences in eukaryotic genomes encode entire proteins or large segments of proteins that lack a well-structured three-dimensional fold, whereas others constitute flexible linkers that have a role in the assembly of macromolecular arrays.
NatureDynamic personalities of proteins
2,452 Citations2007Katherine A. Henzler‐Wildman, Dorothee Kern
The dream is to 'watch' proteins in action in real time at atomic resolution, which requires addition of a fourth dimension, time, to structural biology so that the positions in space and time of all atoms in a protein can be described in detail.
Proteins Structure Function and BioinformaticsPrimary structure effects on peptide group hydrogen exchange
1,922 Citations1993Yawen Bai, John Milne +2 more
The results provide the information necessary to evaluate measured protein NH to ND exchange rates by comparing them with rates to be expected for the same amino acid sequence is unstructured aligo‐ and polypeptides.
NatureSelf-propagation of pathogenic protein aggregates in neurodegenerative diseases
1,601 Citations2013Mathias Jucker, Lary C. Walker
As a unifying pathogenic principle, the prion paradigm suggests broadly relevant therapeutic directions for a large class of currently intractable diseases.
The Journal of Chemical PhysicsMolecular Beams of Macroions
1,558 Citations1968Malcolm Dole, L. L. Mack +4 more
Nature reviews. ImmunologyMonoclonal antibodies: versatile platforms for cancer immunotherapy
1,248 Citations2010Louis M. Weiner, Rishi Surana +1 more
This work states that antibodies exhibit various immunomodulatory properties and, by directly activating or inhibiting molecules of the immune system, antibodies can promote the induction of antitumour immune responses and form the basis for new cancer treatment strategies.
Molecular & Cellular ProteomicsTrypsin Cleaves Exclusively C-terminal to Arginine and Lysine Residues
1,240 Citations2004Jesper V. Olsen, Shao‐En Ong +1 more
This work uses the sub-parts per million mass accuracy of a new ion trap Fourier transform mass spectrometer to achieve more than a 100-fold increased confidence in peptide identification compared with typical ion trap experiments and shows that trypsin cleaves solely C-terminal to arginine and lysine.
Nature Reviews Molecular Cell BiologyChaperone machines for protein folding, unfolding and disaggregation
1,166 Citations2013Helen R. Saibil
The structural basis of their mechanism of action is being unravelled and typically involves massive displacements of 20–30 kDa domains over distances of 20-50 Å and rotations of up to 100°.
Advances in protein chemistryHydrogen Exchange in Proteins
1,132 Citations1966Aase Hvidt, Sigurd O. Nielsen
Quantitative measurements of the rate of hydrogen exchange in a given protein, under specified experimental conditions, provide a multiparameter characterization of the protein conformation (or distribution of conformations) present under these conditions.
Nature ProtocolsIon mobility–mass spectrometry analysis of large protein complexes
1,110 Citations2008Brandon T. Ruotolo, Justin L. P. Benesch +3 more
Within this protocol, general approaches to data interpretation, methods of predicting whether specific model structures for a given protein assembly can be separated by ion mobility, and generalized strategies for data normalization and modeling are covered.
Mass Spectrometry ReviewsFragmentation pathways of protonated peptides
1,102 Citations2004Béla Paizs, Sándor Suhai
It is shown that the 'mobile proton' model of peptide fragmentation can be used to understand the MS/MS spectra of protonated peptides only in a qualitative manner rationalizing differences observed for low-energy collision induced dissociation of peptides having or lacking a mobile proton.
The Journal of Physical ChemistryStructural Information from Ion Mobility Measurements: Effects of the Long-Range Potential
1,031 Citations1996Michael F. Mesleh, Joanna M. Hunter +3 more
Protein ScienceDetermination of amide hydrogen exchange by mass spectrometry: A new tool for protein structure elucidation
1,024 Citations1993Zhongqi Zhang, David L. Smith
Results of this investigation indicate that the combination of protein fragmentation and HPLC‐FABMS is relatively free of constraints associated with other analytical methods used for this purpose and may be a general method for determining hydrogen exchange rates in specific segments of proteins.
Mass Spectrometry ReviewsElectrospray: From ions in solution to ions in the gas phase, what we know now
868 Citations2009P. Kebarle, Udo H. Verkerk
The following processes are considered: Creation of charge droplets at the capillary tip; Electrical potentials required and possibility of gas discharges; Evolution of charged droplets, due to solvent evaporation and Coulomb explosions, to very small droplets that are the precursors of the gas phase ions.
Chemical Society ReviewsHydrogen exchange mass spectrometry for studying protein structure and dynamics
839 Citations2010Lars Konermann, Jingxi Pan +1 more
This tutorial review briefly discusses basic fundamentals of HDX/MS, before highlighting a number of recent developments and applications that facilitate the applicability of HDx/MS to membrane proteins, and to the characterization of short-lived protein folding intermediates.
ScienceNew Tools Provide New Insights in NMR Studies of Protein Dynamics
787 Citations2006Anthony Mittermaier, Lewis E. Kay
A brief overview of some of the new methods in NMR spectroscopy, together with applications that illustrate the level of detail at which protein motions can now be observed, are presented.
Analytical ChemistryUnraveling the Mechanism of Electrospray Ionization
712 Citations2012Lars Konermann, Elias Ahadi +2 more
Electrospray ionization generates intact gas-phase ions from analytes in solution for mass spectrometric investigations and has been proposed for disordered polymers.
Journal of the American Chemical SocietyProbing conformational changes in proteins by mass spectrometry
634 Citations1990Swapan K. Chowdhury, Viswanatham Katta +1 more
The authors describe the first use of mass spectrometry for probing conformational changes in proteins in a manner analogous to that employed in techniques like optical rotary dispersion, circular dichroism, and spectrophotometry.
Angewandte Chemie International EditionElectrospray Wings for Molecular Elephants (Nobel Lecture)
623 Citations2003John B. Fenn
Nature MethodsIdentification of cross-linked peptides from complex samples
598 Citations2012Bing Yang, Yanjie Wu +17 more
NatureThe molecular sociology of the cell
539 Citations2007Carol V. Robinson, Andrej Săli +1 more
Using emerging experimental techniques, such as mass spectrometry of complexes and single-particle cryo-electron microscopy, to complement traditional biochemical and biophysical methods will uncover the molecular architectures, and perhaps even atomic models, of many protein complexes.
Analytica Chimica ActaElectrospray ionization of large multiply charged species proceeds via Dole’s charged residue mechanism
530 Citations2000Juan Fernández de la Mora
PubMedCell biology. A unifying role for prions in neurodegenerative diseases.
488 Citations2012Stanley B. Prusiner
There has been renewed interest in the possibility that the proteins causing neurodegeneration are all prions, which would profoundly influence the development of diagnostics and effective therapies.
Nature MethodsMass spectrometry in high-throughput proteomics: ready for the big time
486 Citations2010Tommy Nilsson, Matthias Mann +4 more
Mass spectrometry has evolved and matured to a level where it is able to assess the complexity of the human proteome and some of the expected challenges ahead and promising strategies for success are discussed.
Annual Review of Analytical ChemistryBiomolecule Analysis by Ion Mobility Spectrometry
485 Citations2008Brian C. Bohrer, Samuel I. Merenbloom +3 more
This review discusses how nonnative states differ in the gas phase compared with solution and presents an overview of early attempts to utilize and manipulate structures in order to develop ion mobility spectrometry as a rapid and sensitive technique for separating complex mixtures of biomolecules prior to mass Spectrometry.
Molecular & Cellular ProteomicsProbing Native Protein Structures by Chemical Cross-linking, Mass Spectrometry, and Bioinformatics
468 Citations2010Alexander Leitner, Thomas Walzthoeni +5 more
The critical steps of chemical cross-linking and its implications for (structural) biology are discussed: reagent design and cross- linking protocols, separation and mass spectrometric analysis of cross-linked samples, dedicated software for data analysis, and the use ofCross-l linking data for computational modeling.
Trends in Pharmacological SciencesDiversity and modularity of G protein-coupled receptor structures
452 Citations2011Vsevolod Katritch, Vadim Cherezov +1 more
Common structural features are reviewed, the scope of structural diversity of GPCRs at different levels of homology is outlined, and a distinct modularity is now being observed between the extracellular (ligand-binding) and intracellular (signaling) regions.
Rapid Communications in Mass SpectrometryConformational changes in proteins probed by hydrogen‐exchange electrospray‐ionization mass spectrometry
450 Citations1991Viswanatham Katta, Brian T. Chait +1 more
Results are presented in which hydrogen-exchange electrospray-ionization mass spectrometry is used to probe conformational changes in bovine ubiquitin induced by the addition of methanol to aqueous acidic solutions of the protein.
Journal of Structural BiologyThe beginning of a beautiful friendship: Cross-linking/mass spectrometry and modelling of proteins and multi-protein complexes
434 Citations2010Juri Rappsilber
Cross-linking in combination with mass spectrometry and bioinformatics will quickly become an indispensable companion of protein and protein complex modelling and a corner-stone of integrated structural biology.
Nature ProtocolsMass spectrometry of intact membrane protein complexes
413 Citations2013Arthur Laganowsky, Eamonn Reading +2 more
The protocol begins with the preparation of the membrane protein complex, enabling not only the direct assessment of stoichiometry, delipidation and quality of the target complex but also the evaluation of the purification strategy.
ScienceStructural Probing of a Protein Phosphatase 2A Network by Chemical Cross-Linking and Mass Spectrometry
384 Citations2012Franz Herzog, Abdullah Kahraman +10 more
This study establishes XL-MS as an integral part of hybrid structural biology approaches for the analysis of endogenous protein complexes by gaining distance restraints on a modular interaction network of protein complexes affinity-purified from human cells by applying an adaptedXL-MS protocol.
Analytical ChemistryHigh-Speed and High-Resolution UPLC Separation at Zero Degrees Celsius
376 Citations2008Thomas E. Wales, Keith E. Fadgen +2 more
Construction and validation of a custom UPLC system for HXMS based on the Waters nanoACQUITY platform and contains a Peltier-cooled module that houses the injection and switching valves, online pepsin digestion column, and C-18 analytical separation column are presented.
Mass Spectrometry ReviewsProbing protein structure by amino acid‐specific covalent labeling and mass spectrometry
370 Citations2008Vanessa Leah Mendoza, Richard W. Vachet
The reagents that are most commonly used in residue-specific modification reactions are described, details about the proper use of these covalent labeling reagents, and information about the specific biochemical problems that have been addressed with covalENT labeling strategies are described.
Rapid Communications in Mass SpectrometryEnhancements in travelling wave ion mobility resolution
368 Citations2011Kevin Giles, Jonathan P. Williams +1 more
The technical advances in the second-generation travelling-wave ion mobility separator result in up to a four-fold increase in mobility resolution, which is demonstrated using two reverse peptides, small ruthenium-containing anticancer drugs, a cisplatin-modified protein and the noncovalent tetradecameric chaperone complex GroEL.
Journal of the American Chemical SocietyComplete Protein Characterization Using Top-Down Mass Spectrometry and Ultraviolet Photodissociation
366 Citations2013Jared Shaw, Wenzong Li +8 more
Near-complete fragmentation of proteins up to 29 kDa is achieved with UVPD including the unambiguous localization of a single residue mutation and several protein modifications on Pin1 (Q13526), a protein implicated in the development of Alzheimer's disease and in cancer pathogenesis.
Nature ChemistryIon mobility–mass spectrometry reveals a conformational conversion from random assembly to β-sheet in amyloid fibril formation
359 Citations2010Christian Bleiholder, Nicholas Dupuis +2 more
This work looks at a series of amyloid forming peptides clipped from larger peptides or proteins associated with disease and provides unambiguous evidence for structural transitions in each of these fibril forming peptide systems establishing the potential of this method for the development of therapeutic agents and drug evaluation.
The Journal of Physical Chemistry BStructural Stability from Solution to the Gas Phase: Native Solution Structure of Ubiquitin Survives Analysis in a Solvent-Free Ion Mobility–Mass Spectrometry Environment
357 Citations2011Thomas Wyttenbach, Michael T. Bowers
The native state of ubiquitin is preserved in the transition from solution to the desolvated state during the ESI process and survives for >100 ms in a 294 K solvent-free environment; the A state is charged more extensively than the native state during ESI and decays more rapidly following ESI.
Journal of Molecular BiologyOligomeric Intermediates in Amyloid Formation: Structure Determination and Mechanisms of Toxicity
335 Citations2012Marcus Fändrich
Focusing primarily on the oligomeric states formed from Alzheimer's disease β-amyloid (Aβ) peptide, this review will make references to other polypeptide systems, highlighting common principles or sequence-specific differences.
The AnalystHow useful is ion mobility mass spectrometry for structural biology? The relationship between protein crystal structures and their collision cross sections in the gas phase
328 Citations2010Ewa Jurneczko, Perdita E. Barran
The relationship between experimental gas-phase conformations and those adopted in crystals is considered and an outlook is given on the application of IM-MS as a tool for structural biology.
Nature MethodsFalse discovery rate estimation for cross-linked peptides identified by mass spectrometry
321 Citations2012Thomas Walzthoeni, Manfred Claassen +6 more
An automated target-decoy strategy and the software tool xProphet are described, which solve the problem of determining false discovery rates of cross-linked peptide assignments for large multicomponent protein complexes.
Journal of the American Chemical SocietyMechanism of Charging and Supercharging Molecules in Electrospray Ionization
320 Citations2003Anthony T. Iavarone, Evan R. Williams
It is demonstrated that in the absence of other factors, the surface tension of the electrospray droplet late in the desolvation process is a significant factor in determining the overall analyte charge.
Journal of the American Chemical SocietyRelative Stability of Hydrogen and Deuterium Bonds
314 Citations1996Steve Scheiner, Martin Čuma
Analytical ChemistryIon Mobility Mass Spectrometry of Peptide Ions: Effects of Drift Gas and Calibration Strategies
313 Citations2012Matthew F. Bush, Iain D. G. Campuzano +1 more
Collision cross section values (Ω) in both He and N(2) gases for 113 peptide ions determined directly from drift times measured in a low-pressure, ambient temperature drift cell with radio-frequency (rf) ion confinement enable the rapid and accurate determination of calibrated Ω for peptides.
Journal of the American Society for Mass SpectrometryHDX Workbench: Software for the Analysis of H/D Exchange MS Data
301 Citations2012Bruce D. Pascal, Scooter Willis +8 more
An integrated desktop program titled HDX Workbench is reported, which facilitates automation, management, visualization, and statistical cross-comparison of large HDX data sets and validated data analysis can be achieved at the rate of generation.
ScienceMass Spectrometry of Intact V-Type ATPases Reveals Bound Lipids and the Effects of Nucleotide Binding
271 Citations2011Min Zhou, Nina Morgner +8 more
It is shown that rotary adenosine triphosphatases (ATPases)/synthases from Thermus thermophilus and Enterococcus hirae can be maintained intact with membrane and soluble subunit interactions preserved in vacuum and can link specific lipid and nucleotide binding with distinct regulatory roles.
Analytical ChemistryHigh Resolution Mass Spectrometry
271 Citations2012Feng Xian, Christopher L. Hendrickson +1 more
This paper presents a meta-analyses of Fourier Transform Mass Analyzers for time-of-Flight (TOF) resolution and accuracy and describes the efforts to characterize the properties of the Fourier transform process.
FEBS JournalCryo‐electron microscopy – a primer for the non‐microscopist
270 Citations2012Jacqueline L.S. Milne, Mario J. Borgnia +8 more
An overview of emerging themes in the application of this technology to investigate diverse questions in biology and medicine is provided, including a description of how the structural information obtained by cryo‐EM is deposited and archived in a publicly accessible database.
Journal of the American Chemical SocietyCharge-State Dependent Compaction and Dissociation of Protein Complexes: Insights from Ion Mobility and Molecular Dynamics
269 Citations2012Zoe Hall, Argyris Politis +3 more
It is found that all four macromolecular complexes retain their native-like topologies at low energy during collisional activation, using ion mobility-mass spectrometry (IM-MS), and this has implications for further studies as well as for understanding the process of CID and for applications to gas-phase structural biology more generally.
StructureFrom Sequence and Forces to Structure, Function, and Evolution of Intrinsically Disordered Proteins
267 Citations2013Julie D. Forman‐Kay, Tanja Mittag
A historical perspective on the investigation of IDPs is provided and the sequence features and physical forces that underlie their unique structural, functional, and evolutionary properties are summarized.
Nature ChemistryInterrogating viral capsid assembly with ion mobility–mass spectrometry
266 Citations2010Charlotte Uetrecht, Ioana Barbu +3 more
Small oligomers of Hepatitis B virus and norovirus are characterised under equilibrium conditions using native ion mobility mass spectrometry and the intermediates exhibit sheet-like structures suggesting that they are assembly competent, and propose pathways for the formation of both capsids.
Expert Review of ProteomicsDifferential hydrogen/deuterium exchange mass spectrometry analysis of protein–ligand interactions
262 Citations2011Michael J. Chalmers, Scott A. Busby +3 more
How HDX analysis of protein–ligand interactions has had an impact on biology and drug discovery is summarized.
Current Opinion in Chemical BiologyAspects of native proteins are retained in vacuum
241 Citations2006Brandon T. Ruotolo, Carol V. Robinson
The eventual outcomes of this research will not only increase the number of applications of mass spectrometry to structural biology, but will also enhance the understanding of the interactions important for maintaining protein complexes in the absence of bulk solvent.
Journal of the American Society for Mass SpectrometryReliable Determinations of Protein–Ligand Interactions by Direct ESI-MS Measurements. Are We There Yet?
235 Citations2012Elena N. Kitova, Amr El-Hawiet +2 more
The implementation of the direct ESI-MS assay for the determination of protein–ligand binding stoichiometry and affinity is described and common sources of error encountered with these measurements are outlined.
Nature Structural & Molecular BiologyStructural organization of brain-derived mammalian prions examined by hydrogen-deuterium exchange
222 Citations2011Vytautas Smirnovas, Gerald S. Baron +4 more
The data indicate that, contrary to popular models, prion-protein conversion involves refolding of the entire region from residue ~80–90 to the C-terminus, which in PrPSc consists of β-strands and relatively short turns and/or loops, with no native α-helices present.
Chemical Society ReviewsPrinciples of electron capture and transfer dissociation mass spectrometry applied to peptide and protein structure analysis
221 Citations2013Konstantin O. Zhurov, Luca Fornelli +3 more
This tutorial review describes the principles and practices of electron capture and transfer dissociation (ECD/ETD or ExD) mass spectrometry employed for peptide and protein structure analysis and provides practical guidelines for peptides de novo sequencing with ExD MS.
Analytical ChemistryFast Photochemical Oxidation of Protein Footprints Faster than Protein Unfolding
217 Citations2009Brian Gau, Joshua S. Sharp +2 more
Fast photochemical oxidation of proteins is applied to three oxidation-sensitive proteins and it is found that the distribution of modification (oxidation) states is Poisson when a scavenger is present, consistent with a single conformation protein modification model.
Mass Spectrometry ReviewsCrosslinking combined with mass spectrometry for structural proteomics
210 Citations2010Evgeniy V. Petrotchenko, Christoph H. Borchers
Critical features of crosslinking reagents for optimum mass spectrometric performance, such as isotopic coding, cleavability, affinity groups, structure of the linkers, and reactive groups, are assessed.
Drug Discovery TodayHydrogen/deuterium exchange mass spectrometry for probing higher order structure of protein therapeutics: methodology and applications
201 Citations2013Hui Wei, Jingjie Mo +6 more
In this review, HDX-MS based workflows designed for protein therapeutic discovery and development processes are presented, focusing on the specific applications of epitope mapping for protein/drug interactions and biopharmaceutical comparability studies.
Angewandte Chemie International EditionStudying 18 MDa Virus Assemblies with Native Mass Spectrometry
187 Citations2013Joost Snijder, Rebecca Rose +3 more
Journal of the American Society for Mass SpectrometryAnalysis of Overlapped and Noisy Hydrogen/Deuterium Exchange Mass Spectra
186 Citations2013Miklós Guttman, David D. Weis +2 more
The use of binomial distribution fitting with asymmetric linear squares regression for calculating the accurate deuterium content for mass envelopes of low signal or that contain significant overlap is described.
Expert Review of ProteomicsIon mobility–mass spectrometry for structural proteomics
178 Citations2012Yueyang Zhong, Suk‐Joon Hyung +1 more
The technology, approaches and data that have led to this dramatic shift in use, including emerging trends such as the integration of ion mobility–mass spectrometry data with more classical (e.g., ‘bottom-up’) proteomics approaches for the rapid structural characterization of protein networks are highlighted.
Proceedings of the National Academy of SciencesStepwise protein folding at near amino acid resolution by hydrogen exchange and mass spectrometry
177 Citations2013Wenbing Hu, Benjamin T. Walters +5 more
Analytical ChemistryCombined Charged Residue-Field Emission Model of Macromolecular Electrospray Ionization
175 Citations2008Christopher J. Hogan, James A. Carroll +3 more
Examination of rate expressions for solvent evaporation and charge-carrier emission demonstrates that the newly proposed model for ESI is consistent with previously reported ion-emission kinetics, suggesting opportunities for understanding and applying ESI-MS.
Rapid Communications in Mass SpectrometrySpecificity of immobilized porcine pepsin in H/D exchange compatible conditions
174 Citations2008Yoshitomo Hamuro, Stephen J. Coales +3 more
While the specificity of pepsin was similar to that previously observed, higher selectivity was observed in the present study due to less experimental variation in the conditions used to generate the database.
PLoS ONECross-Link Guided Molecular Modeling with ROSETTA
173 Citations2013Abdullah Kahraman, Franz Herzog +4 more
Three workflows for incorporating distance restraints generated by chemical cross-linking and mass spectrometry into ROSETTA protocols for comparative and de novo modeling and protein-protein docking are introduced and the cross-link validation and visualization software Xwalk facilitates successful cross- link data integration.
Analytica Chimica ActaProbing protein interactions with hydrogen/deuterium exchange and mass spectrometry—A review
165 Citations2012Andrew J. Percy, Martial Rey +2 more
This review presents the exchange method in the context of interaction analysis, and offers a chemical labeling strategy suitable for tracking changes in "dynamic topography" and thus represents a powerful means of monitoring protein structure-function relationships.
Journal of the American Society for Mass SpectrometryNew reagents for increasing ESI multiple charging of proteins and protein complexes
162 Citations2009Shirley H. Lomeli, Ivory X. Peng +3 more
The addition of m-nitrobenzyl alcohol was shown to enhance multiple charging of native proteins and noncovalent protein complexes in electrospray ionization (ESI) mass spectra and additional new reagents have been found to “supercharge” proteins from nondenaturing solutions.
StructureTwenty Years of Gas Phase Structural Biology
160 Citations2013Julien Marcoux, Carol V. Robinson
Recent progress in the study of protein complexes is considered, focusing particularly on complexes extracted from membranes, and future prospects for gas phase structural biology are outlined.
Analytical ChemistryNative Electrospray and Electron-Capture Dissociation FTICR Mass Spectrometry for Top-Down Studies of Protein Assemblies
157 Citations2011Hao Zhang, Weidong Cui +3 more
An approach to study protein assemblies that integrates electron-capture dissociation (ECD), native ESI, and FTICR mass spectrometry (12 T) provides not only top-down proteomics information of the complex subunits but also structural insights complementary to those obtained by ion mobility.
Nature MethodsDetergent-free mass spectrometry of membrane protein complexes
155 Citations2013Jonathan T. S. Hopper, Yvonne Ting-Chun Yu +10 more
It is demonstrated that oligomeric complexes or proteins requiring defined lipid environments are stabilized to a greater extent in the absence of detergent.
Proceedings of the National Academy of SciencesAllosteric mechanisms can be distinguished using structural mass spectrometry
152 Citations2013Andrey Dyachenko, Ranit Gruber +3 more
It is demonstrated that structural MS offers a way to break this impasse by providing the full distribution of ligand-bound states of a protein complex, and it is possible to determine all the binding constants of a ligand to a highly multimeric cooperative system, and thereby infer its allosteric mechanism.
Proceedings of the National Academy of SciencesProtein hydrogen exchange at residue resolution by proteolytic fragmentation mass spectrometry analysis
151 Citations2013Zhong-Yuan Kan, Benjamin T. Walters +2 more
This paper shows how hydrogen exchange–mass spectrometry data can be deconvolved to obtain direct protein structural information at amino acid resolution and uses an iterative optimization program that integrates recent progress in multiple peptide acquisition together with previously unexamined isotopic envelope-shape information and a site-resolved back-exchange correction.
Analytical ChemistryCollisions or Electrons? Protein Sequence Analysis in the 21st Century
150 Citations2009Joshua J. Coon
How dissociation is effected determines the upstream sample handling whereas the spectral features it produces regulate the downstream informatics approach.
Biochimica et Biophysica Acta (BBA) - Proteins and ProteomicsAccessing the reproducibility and specificity of pepsin and other aspartic proteases
149 Citations2012Joomi Ahn, Min‐Jie Cao +2 more
It was found that the number of reproducible peptides produced during pepsin digestion becomes constant above 5-6 replicate digestions, and a new aspartic protease from the stomach of the rice field eel was investigated and compared digestion efficiency and specificity to porcine pepin and aspergillopepsin.
Journal of the American Society for Mass SpectrometryElectron capture/transfer versus collisionally activated/induced dissociations: Solo or duet?
146 Citations2008Roman A. Zubarev, Alexander R. Zubarev +1 more
This critical analysis presents arguments for the combined use of ExD with the conventional low-energy collisional excitation CID/CAD (CxD) and argues that the database search, a key technology in MS/MS-based proteomics, is vulnerable with respect to the incomplete sequence information obtainable with either of the techniques.
Journal of the American Society for Mass SpectrometryProtein Conformation and Supercharging with DMSO from Aqueous Solution
145 Citations2011Harry J. Sterling, James S. Prell +2 more
Results provide additional evidence that the origin of supercharging from aqueous solution is the result of chemical and/or thermal denaturation that occurs in the ESI droplet as the concentration of these supercharging reagents increases, and that proton transfer reactivity does not play a significant role in the charge enhancement observed.
StructureLigand-Dependent Perturbation of the Conformational Ensemble for the GPCR β2 Adrenergic Receptor Revealed by HDX
143 Citations2011Graham M. West, Ellen Y. T. Chien +5 more
The regional plasticity of the receptor is highlighted and characterizes unique conformations spanning the entire receptor sequence stabilized by functionally selective ligands, all of which differ from the profile for the apo receptor.
Journal of ProteomicsQuantitative cross-linking/mass spectrometry using isotope-labelled cross-linkers
142 Citations2013Lutz Fischer, Zhuo A. Chen +1 more
Journal of The Royal Society InterfaceTwo decades of studying non-covalent biomolecular assemblies by means of electrospray ionization mass spectrometry
141 Citations2012Gillian R. Hilton, Justin L. P. Benesch
This work charts the remarkable rise of MS and its application to biomolecular complexes over the last two decades and addresses questions of shape, inter-subunit connectivity and protein dynamics.
Chemical Society ReviewsMass spectrometry based tools to investigate protein–ligand interactions for drug discovery
139 Citations2012Kamila J. Pacholarz, Rachel A. Garlish +2 more
How conjunction of mass spectrometry with related techniques and methodologies such as ion mobility, hydrogen-deuterium exchange (HDX), protein footprinting or chemical cross-linking can provide us with structural information useful for drug development is discussed.
Journal of Proteome Research<i>In Vivo</i> Protein Interaction Network Identified with a Novel Real-Time Cross-Linked Peptide Identification Strategy
138 Citations2013Chad R. Weisbrod, Juan D. Chavez +4 more
ReACT enables the first view of these interactions inside cells, and the results acquired with this method suggest cross-linking can play a major role in future efforts to map the interactome in cells.
Analytical ChemistryCharge-Surface Correlation in Electrospray Ionization of Folded and Unfolded Proteins
138 Citations2011Lorenzo Testa, Stefania Brocca +1 more
It is found that the charge-to-surface relation holds for proteins in the unfolded state, free from solvent effects, and can be used to predict the average solvent accessibility and, hence, the state of folding of unknown proteins from ESI-MS data.
PLoS ONEIntegrating Ion Mobility Mass Spectrometry with Molecular Modelling to Determine the Architecture of Multiprotein Complexes
136 Citations2010Argyris Politis, Ah Young Park +4 more
An integrative computational method that uses molecular modelling, ion mobility-mass spectrometry (IM-MS) and incomplete atomic structures, usually from X-ray crystallography, to generate models of the subunit architecture of protein complexes is presented.
Proceedings of the National Academy of SciencesDefining a protective epitope on factor H binding protein, a key meningococcal virulence factor and vaccine antigen
134 Citations2013E. Malito, Agnese Faleri +25 more
Data show that linear epitope mapping techniques provide useful but incomplete descriptions of B-cell epitopes, indicating that increased efforts to fully characterize antigen–antibody interfaces are required to understand and design effective immunogens.
Molecular & Cellular ProteomicsProtein Interactions, Post-translational Modifications and Topologies in Human Cells
133 Citations2013Juan D. Chavez, Chad R. Weisbrod +3 more
The results presented here provide new details on the structures of known multi-protein complexes as well as evidence for new protein-protein interactions.
Journal of Structural BiologyClpP: A structurally dynamic protease regulated by AAA+ proteins
131 Citations2012John A. Alexopoulos, Alba Guarné +1 more
Current understanding of the conformational changes that ClpA or ClpX induce in ClpP to open the axial gate and increase substrate accessibility into the degradation chamber is reviewed.
Journal of the American Society for Mass SpectrometryMany Overlapping Peptides for Protein Hydrogen Exchange Experiments by the Fragment Separation-Mass Spectrometry Method
130 Citations2011Leland Mayne, Zhong-Yuan Kan +4 more
Operations which, when applied to four different proteins ranging in size from 140 to 908 residues, routinely provides hundreds of useful unique peptides, covering the entire protein length many times over.
Angewandte Chemie International EditionElectrostatic Stabilization of a Native Protein Structure in the Gas Phase
129 Citations2010Kathrin Breuker, Sven Brüschweiler +1 more
Electron capture dissociation data on the gas-phase structures of the three-helix bundle protein KIX5 indicate substantial preservation of the native solution structure on a timescale of at least 4 s, and demonstrate that in the gas phase, the most stable regions are those stabilized by salt bridges and ionic hydrogen bonds.
Journal of the American Society for Mass SpectrometryExMS: Data Analysis for HX-MS Experiments
127 Citations2011Zhong-Yuan Kan, Leland Mayne +2 more
ExMS automatically scans through high resolution MS data to find the individual isotopic peaks and isotopic envelopes of a list of peptides previously identified by MS/MS and performs a number of tests to ensure correct identification in spite of peptide overlap.
The Journal of Physical Chemistry BTandem Differential Mobility Analysis-Mass Spectrometry Reveals Partial Gas-Phase Collapse of the GroEL Complex
124 Citations2011Christopher J. Hogan, Brandon T. Ruotolo +2 more
The gas-phase structure of the GroEL complex as electrosprayed is substantially more compact than the corresponding X-ray crystal structure, based on prior and new numerical modeling accounting for multiple scattering events via exact hard-sphere scattering calculations.
Analytical ChemistryImproved Protein Hydrogen/Deuterium Exchange Mass Spectrometry Platform with Fully Automated Data Processing
123 Citations2012Zhongqi Zhang, Aming Zhang +1 more
The improved HDX MS platform with fully automated data processing is described, which significantly reduces systematic and random errors in the measurement by introducing two types of corrections in HDX data analysis.
Proteins Structure Function and BioinformaticsProtein folding kinetics by combined use of rapid mixing techniques and NMR observation of individual amide protons
121 Citations1986Heinrich Röder, Kurt Wüthrich
The basic pancreatic trypsin inhibitor was applied by using rapid mixing techniques and 1H NMR to provide site‐resolved kinetic information on the early phases of protein structure acquisition.
ScienceIntrinsically Disordered Protein Threads Through the Bacterial Outer-Membrane Porin OmpF
121 Citations2013Nicholas G. Housden, Jonathan T. S. Hopper +9 more
This work has studied how the bacteriocin colicin E9 (ColE9) assembles a cytotoxic translocon at the surface of Escherichia coli that incorporates the trimeric porin OmpF.
Analytical ChemistryFast Photochemical Oxidation of Proteins for Epitope Mapping
120 Citations2011Lisa M. Jones, Justin B. Sperry +2 more
This study reports the use of footprinting via fast photochemical oxidation of proteins (FPOP) with OH radicals to characterize the epitope of the serine protease thrombin, the first time oxidative labeling has been used for epitope mapping.
StructureStructural Modeling of Heteromeric Protein Complexes from Disassembly Pathways and Ion Mobility-Mass Spectrometry
119 Citations2012Zoe Hall, Argyris Politis +1 more
An assessment of an emerging structural technique, ion mobility-mass spectrometry (IM-MS), and the use of collision cross-sections (CCSs), derived from IM-MS, as restraints for structure characterization of heteromeric protein assemblies are provided.
Analytical ChemistryStructural Mass Spectrometry of Proteins Using Hydroxyl Radical Based Protein Footprinting
119 Citations2011Liwen Wang, Mark R. Chance
The overall technology is described and several examples of how hydroxyl radical based footprinting MS can be used to map interfaces, evaluate protein structure, and identify ligand dependent conformational changes in proteins are described.
Journal of the American Chemical SocietyA General Mass Spectrometry-Based Assay for the Quantitation of Protein−Ligand Binding Interactions in Solution
118 Citations2002Kendall D. Powell, Sina Ghaemmaghami +4 more
Proceedings of the National Academy of SciencesPulsed hydrogen–deuterium exchange mass spectrometry probes conformational changes in amyloid beta (Aβ) peptide aggregation
117 Citations2013Ying Zhang, Don L. Rempel +4 more
An MS-based biophysical approach to the formation of soluble aggregates of the Aβ42 peptide, the proposed causative agent in Alzheimer’s disease, incorporates pulsed hydrogen–deuterium exchange coupled with MS analysis and reveals that the center region of A β42 is first to aggregate, followed by the C and N termini.
Journal of the American Society for Mass SpectrometryHydrogen Exchange Mass Spectrometry: Are We Out of the Quicksand?
110 Citations2012Roxana E. Iacob, John R. Engen
This critical insight addresses the “issues” of hydrogen exchange mass spectrometry and explores several broad questions including, have the limitations of HX MS been surmounted and has HXMS achieved “indispensable” status in the pantheon of protein structural analysis tools.
…