Protein Dynamics in Solution by Quantitative Crosslinking/Mass Spectrometry

The dynamics of protein structures and their interactions are responsible for many cellular processes. The rearrangements and interactions of proteins, which are often transient, occur in solution and may require a biological environment that is difficult to maintain in traditional structural biological approaches. Quantitative crosslinking/mass spectrometry (QCLMS) has emerged as an excellent method to fill this gap. Numerous recent applications of the technique have demonstrated that protein dynamics can now be studied in solution at sufficient resolution to gain valuable biological insights, suggesting that extending these investigations to native environments is possible. These breakthroughs have been based on the maturation of CLMS at large, and its recent fusion with quantitative proteomics. We provide here an overview of the current state of the technique, the available workflows and their applications, and remaining challenges.

[1]  Otto Hudecz,et al.  Structural prediction of protein models using distance restraints derived from cross-linking mass spectrometry data , 2018, Nature Protocols.

[2]  D. Gerloff,et al.  Three-dimensional topology of the SMC2/SMC4 subcomplex from chicken condensin I revealed by cross-linking and molecular modelling , 2015, Open Biology.

[3]  Hao Chi,et al.  pQuant improves quantitation by keeping out interfering signals and evaluating the accuracy of calculated ratios. , 2014, Analytical chemistry.

[4]  Natalie I. Tasman,et al.  A Cross-platform Toolkit for Mass Spectrometry and Proteomics , 2012, Nature Biotechnology.

[5]  Oliver M. Bernhardt,et al.  Extending the Limits of Quantitative Proteome Profiling with Data-Independent Acquisition and Application to Acetaminophen-Treated Three-Dimensional Liver Microtissues* , 2015, Molecular & Cellular Proteomics.

[6]  Ruedi Aebersold,et al.  A mass spectrometry-based hybrid method for structural modelling of protein complexes , 2014, Nature Methods.

[7]  A. Sali,et al.  Structure of Complement C3(H2O) Revealed By Quantitative Cross-Linking/Mass Spectrometry And Modeling* , 2016, Molecular & Cellular Proteomics.

[8]  Devin K. Schweppe,et al.  Large-Scale and Targeted Quantitative Cross-Linking MS Using Isotope-Labeled Protein Interaction Reporter (PIR) Cross-Linkers. , 2017, Journal of proteome research.

[9]  M. Mann,et al.  MaxQuant enables high peptide identification rates, individualized p.p.b.-range mass accuracies and proteome-wide protein quantification , 2008, Nature Biotechnology.

[10]  Lutz Fischer,et al.  A Study into the Collision-induced Dissociation (CID) Behavior of Cross-Linked Peptides , 2015, Molecular & Cellular Proteomics.

[11]  Otto Hudecz,et al.  Comprehensive Cross-Linking Mass Spectrometry Reveals Parallel Orientation and Flexible Conformations of Plant HOP2-MND1. , 2015, Journal of proteome research.

[12]  Edward L. Huttlin,et al.  MultiNotch MS3 Enables Accurate, Sensitive, and Multiplexed Detection of Differential Expression across Cancer Cell Line Proteomes , 2014, Analytical chemistry.

[13]  Carol V. Robinson,et al.  Comparative cross-linking and mass spectrometry of an intact F-type ATPase suggest a role for phosphorylation , 2013, Nature Communications.

[14]  Lan Huang,et al.  Gln40 deamidation blocks structural reconfiguration and activation of SCF ubiquitin ligase complex by Nedd8 , 2015, Nature Communications.

[15]  Lars Malmström,et al.  xTract: software for characterizing conformational changes of protein complexes by quantitative cross-linking mass spectrometry , 2015, Nature Methods.

[16]  Ruedi Aebersold,et al.  Identification of cross-linked peptides from large sequence databases , 2008, Nature Methods.

[17]  A. Oliveira,et al.  Global analysis of protein structural changes in complex proteomes , 2014, Nature Biotechnology.

[18]  R. Aebersold,et al.  Crosslinking and Mass Spectrometry: An Integrated Technology to Understand the Structure and Function of Molecular Machines. , 2016, Trends in biochemical sciences.

[19]  K. Parker,et al.  Multiplexed Protein Quantitation in Saccharomyces cerevisiae Using Amine-reactive Isobaric Tagging Reagents*S , 2004, Molecular & Cellular Proteomics.

[20]  Martin Strohalm,et al.  Mapping protein structural changes by quantitative cross-linking. , 2015, Methods.

[21]  Jürgen Cox,et al.  Quantitative Cross-linking/Mass Spectrometry Using Isotope-labeled Cross-linkers and MaxQuant* , 2016, Molecular & Cellular Proteomics.

[22]  Lutz Fischer,et al.  In-Search Assignment of Monoisotopic Peaks Improves the Identification of Cross-Linked Peptides , 2018, bioRxiv.

[23]  Yang Zhang,et al.  The I-TASSER Suite: protein structure and function prediction , 2014, Nature Methods.

[24]  Brendan MacLean,et al.  Skyline: an open source document editor for creating and analyzing targeted proteomics experiments , 2010, Bioinform..

[25]  Albert J R Heck,et al.  Proteome-wide profiling of protein assemblies by cross-linking mass spectrometry , 2015, Nature Methods.

[26]  Michael Götze,et al.  Optimizing the enrichment of cross-linked products for mass spectrometric protein analysis. , 2012, Rapid communications in mass spectrometry : RCM.

[27]  Juri Rappsilber,et al.  On the Reproducibility of Label-Free Quantitative Cross-Linking/Mass Spectrometry , 2017, Journal of The American Society for Mass Spectrometry.

[28]  Markus Hsi-Yang Fritz,et al.  Genetic code expansion for multiprotein complex engineering , 2016, Nature Methods.

[29]  Gordon A Anderson,et al.  Informatics strategies for large-scale novel cross-linking analysis. , 2007, Journal of proteome research.

[30]  Tomasz Heyduk,et al.  Measuring protein conformational changes by FRET/LRET. , 2002, Current opinion in biotechnology.

[31]  B. Luke,et al.  18O stable isotope labeling in MS-based proteomics. , 2009, Briefings in functional genomics & proteomics.

[32]  G. Anderson,et al.  Identification of Protein-Protein Interactions and Topologies in Living Cells with Chemical Cross-linking and Mass Spectrometry*S , 2009, Molecular & Cellular Proteomics.

[33]  Paul R. Selvin,et al.  The renaissance of fluorescence resonance energy transfer , 2000, Nature Structural Biology.

[34]  Ben M. Webb,et al.  Putting the Pieces Together: Integrative Modeling Platform Software for Structure Determination of Macromolecular Assemblies , 2012, PLoS biology.

[35]  Mårten Larsson,et al.  A General Method for Targeted Quantitative Cross-Linking Mass Spectrometry , 2016, PloS one.

[36]  R. Aebersold,et al.  Expanding the Chemical Cross-Linking Toolbox by the Use of Multiple Proteases and Enrichment by Size Exclusion Chromatography , 2012, Molecular & Cellular Proteomics.

[37]  Ruth Nussinov,et al.  PatchDock and SymmDock: servers for rigid and symmetric docking , 2005, Nucleic Acids Res..

[38]  J. Rappsilber,et al.  Quantitative cross-linking/mass spectrometry reveals subtle protein conformational changes , 2016, bioRxiv.

[39]  Philipp Selenko,et al.  Structural Biology outside the box-inside the cell. , 2017, Current opinion in structural biology.

[40]  Shiyong Wu,et al.  Probing Protein 3D Structures and Conformational Changes Using Electrochemistry-Assisted Isotope Labeling Cross-Linking Mass Spectrometry , 2016, Journal of the American Society for Mass Spectrometry.

[41]  C. D. de Koster,et al.  Selective enrichment of azide-containing peptides from complex mixtures. , 2009, Journal of proteome research.

[42]  J. Rappsilber,et al.  Cross-linking mass spectrometry: methods and applications in structural, molecular and systems biology , 2018, Nature Structural & Molecular Biology.

[43]  David Fenyö,et al.  A modular cross-linking approach for exploring protein interactions. , 2002, Journal of the American Chemical Society.

[44]  Juri Rappsilber,et al.  A Single α Helix Drives Extensive Remodeling of the Proteasome Lid and Completion of Regulatory Particle Assembly , 2015, Cell.

[45]  Jimmy K. Eng,et al.  Quantitative interactome analysis reveals a chemoresistant edgotype , 2015, Nature Communications.

[46]  John R. Engen,et al.  Analysis of protein conformation and dynamics by hydrogen/deuterium exchange MS. , 2009, Analytical chemistry.

[47]  Olivier Langella,et al.  MassChroQ: A versatile tool for mass spectrometry quantification , 2011, Proteomics.

[48]  Devin K Schweppe,et al.  In Vivo Conformational Dynamics of Hsp90 and Its Interactors. , 2016, Cell chemical biology.

[49]  W. Baumeister,et al.  An integrated workflow for crosslinking mass spectrometry , 2018, bioRxiv.

[50]  Reinout Raijmakers,et al.  Multiplex peptide stable isotope dimethyl labeling for quantitative proteomics , 2009, Nature Protocols.

[51]  Bill X. Huang,et al.  Probing Akt-inhibitor interaction by chemical cross-linking and mass spectrometry , 2009, Journal of the American Society for Mass Spectrometry.

[52]  J. Rappsilber,et al.  Complement Evasion Mediated by Enhancement of Captured Factor H: Implications for Protection of Self-Surfaces from Complement , 2015, The Journal of Immunology.

[53]  Chao Liu,et al.  Trifunctional cross-linker for mapping protein-protein interaction networks and comparing protein conformational states , 2016, eLife.

[54]  Carla Schmidt,et al.  A comparative cross-linking strategy to probe conformational changes in protein complexes , 2014, Nature Protocols.

[55]  M. Sisido,et al.  FRET analysis of protein conformational change through position-specific incorporation of fluorescent amino acids , 2006, Nature Methods.

[56]  B. Domon,et al.  Targeted Proteomic Quantification on Quadrupole-Orbitrap Mass Spectrometer* , 2012, Molecular & Cellular Proteomics.

[57]  L. Banci,et al.  In-cell NMR: a topical review , 2017, IUCrJ.

[58]  T. Sixma,et al.  Identification of cross-linked peptides for protein interaction studies using mass spectrometry and 18O labeling. , 2002, Analytical chemistry.

[59]  Juri Rappsilber,et al.  Quantitative cross-linking/mass spectrometry using isotope-labelled cross-linkers☆ , 2013, Journal of proteomics.

[60]  Andrew H. Thompson,et al.  Tandem mass tags: a novel quantification strategy for comparative analysis of complex protein mixtures by MS/MS. , 2003, Analytical chemistry.

[61]  S. Mohammed,et al.  eIF2 interactions with initiator tRNA and eIF2B are regulated by post-translational modifications and conformational dynamics , 2015, Cell Discovery.

[62]  Juri Rappsilber,et al.  A generic solution for quantifying cross-linked peptides using software Skyline , 2018 .

[63]  Y. Nesmelov.  Protein structural dynamics revealed by site-directed spin labeling and multifrequency EPR. , 2014, Methods in molecular biology.

[64]  Andrea Sinz,et al.  Cross-Linking/Mass Spectrometry for Studying Protein Structures and Protein-Protein Interactions: Where Are We Now and Where Should We Go from Here? , 2018, Angewandte Chemie.

[65]  C. Dominguez,et al.  HADDOCK: a protein-protein docking approach based on biochemical or biophysical information. , 2003, Journal of the American Chemical Society.

[66]  P. Cramer,et al.  Architecture of the RNA polymerase II–TFIIF complex revealed by cross-linking and mass spectrometry , 2010, EMBO Journal.

[67]  Lan Huang,et al.  Cross-Linking Mass Spectrometry: An Emerging Technology for Interactomics and Structural Biology. , 2018, Analytical chemistry.

[68]  Derek J. Bailey,et al.  Parallel Reaction Monitoring for High Resolution and High Mass Accuracy Quantitative, Targeted Proteomics* , 2012, Molecular & Cellular Proteomics.

[69]  M. Steinmetz,et al.  Isotope-tagged cross-linking reagents. A new tool in mass spectrometric protein interaction analysis. , 2001, Analytical chemistry.

[70]  M. Mann,et al.  Stable Isotope Labeling by Amino Acids in Cell Culture, SILAC, as a Simple and Accurate Approach to Expression Proteomics* , 2002, Molecular & Cellular Proteomics.

[71]  Lars Malmström,et al.  Cross-Link Guided Molecular Modeling with ROSETTA , 2013, PloS one.

[72]  I. André,et al.  Mapping the Ca(2+) induced structural change in calreticulin. , 2016, Journal of proteomics.

[73]  S. Gygi,et al.  Absolute quantification of proteins and phosphoproteins from cell lysates by tandem MS , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[74]  Martin Strohalm,et al.  mMass 3: a cross-platform software environment for precise analysis of mass spectrometric data. , 2010, Analytical chemistry.

[75]  J. Rappsilber,et al.  Optimizing the Parameters Governing the Fragmentation of Cross-Linked Peptides in a Tribrid Mass Spectrometer , 2017, Analytical chemistry.

[76]  Jason Lanman,et al.  Synthesis of biotin-tagged chemical cross-linkers and their applications for mass spectrometry. , 2009, Rapid communications in mass spectrometry : RCM.

[77]  Lan Huang,et al.  Developing a Multiplexed Quantitative Cross-Linking Mass Spectrometry Platform for Comparative Structural Analysis of Protein Complexes. , 2016, Analytical chemistry.