Mass spectrometry supported determination of protein complex structure.

Virtually all the biological processes are controlled and catalyzed by proteins which are, in many cases, in complexes with other proteins. Therefore, understanding the architecture and structure of protein complexes is critical to understanding their biological role and function. Traditionally, high-resolution data for structural analysis of proteins or protein complexes have been generated by the powerful methods of X-ray crystallography and nuclear magnetic resonance (NMR) spectroscopy. More recently, mass spectrometry (MS)-based methods have been developed that provide low-resolution structural information, which contributes to the determination of the native structure of protein complexes that have remained refractory to the high-resolution methods. Native MS and affinity purification coupled with MS (AP-MS) have been used to characterize the composition, stoichiometry and connectivity of protein complexes. Chemical cross-linking MS (CX-MS) provides protein-protein interaction data supplemented with distance information that indicates residues that are in close spatial proximity in the native protein structure. Hydrogen-deuterium exchange combined with MS has been used to map protein-protein binding sites. Here, we focus on recent developments in CX-MS and native MS and their application to challenging problems in structural biology.

[1]  Chad R. Weisbrod,et al.  Architecture and dynamics of an A-kinase anchoring protein 79 (AKAP79) signaling complex , 2011, Proceedings of the National Academy of Sciences.

[2]  L. Kay,et al.  Quaternary dynamics and plasticity underlie small heat shock protein chaperone function , 2010, Proceedings of the National Academy of Sciences.

[3]  A. Sali,et al.  The molecular sociology of the cell , 2007, Nature.

[4]  C. Robinson,et al.  Heterogeneity and dynamics in the assembly of the Heat Shock Protein 90 chaperone complexes , 2011, Proceedings of the National Academy of Sciences.

[5]  Gabriel C. Lander,et al.  Complete subunit architecture of the proteasome regulatory particle , 2011, Nature.

[6]  David R Goodlett,et al.  Chemical cross‐linking, mass spectrometry, and in silico modeling of proteasomal 20S core particles of the haloarchaeon Haloferax volcanii , 2012, Proteomics.

[7]  Ning Zhang,et al.  Protein cross-linking analysis using mass spectrometry, isotope-coded cross-linkers, and integrated computational data processing. , 2006, Journal of proteome research.

[8]  E. Morris,et al.  Molecular model of the human 26S proteasome. , 2012, Molecular cell.

[9]  Friedrich Förster,et al.  False discovery rate estimation for cross-linked peptides identified by mass spectrometry , 2012, Nature Methods.

[10]  Michael R Hoopmann,et al.  Cross-linking Measurements of In Vivo Protein Complex Topologies* , 2011, Molecular & Cellular Proteomics.

[11]  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.

[12]  Christoph H Borchers,et al.  Crosslinking combined with mass spectrometry for structural proteomics. , 2010, Mass spectrometry reviews.

[13]  R. Aebersold,et al.  Insights into EB1 structure and the role of its C-terminal domain for discriminating microtubule tips from the lattice , 2011, Molecular biology of the cell.

[14]  Ruedi Aebersold,et al.  Corrigendum: Identification of cross-linked peptides from large sequence databases , 2008 .

[15]  Brandon T Ruotolo,et al.  Mass spectrometry: come of age for structural and dynamical biology. , 2011, Current opinion in structural biology.

[16]  A. Barabasi,et al.  Network biology: understanding the cell's functional organization , 2004, Nature Reviews Genetics.

[17]  M. Mann,et al.  A generic strategy to analyze the spatial organization of multi-protein complexes by cross-linking and mass spectrometry. , 2000, Analytical chemistry.

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

[19]  Paul D. Adams,et al.  Crystal Structures of a Group II Chaperonin Reveal the Open and Closed States Associated with the Protein Folding Cycle*♦ , 2010, The Journal of Biological Chemistry.

[20]  Friedrich Förster,et al.  Structure of the 26S proteasome from Schizosaccharomyces pombe at subnanometer resolution , 2010, Proceedings of the National Academy of Sciences.

[21]  Friedrich Förster,et al.  Near-atomic resolution structural model of the yeast 26S proteasome , 2012, Proceedings of the National Academy of Sciences.

[22]  Carol V Robinson,et al.  Micelles Protect Membrane Complexes from Solution to Vacuum , 2008, Science.

[23]  R. Aebersold,et al.  Analysis of protein complexes using mass spectrometry , 2007, Nature Reviews Molecular Cell Biology.

[24]  Pierre Baldi,et al.  Mapping the Structural Topology of the Yeast 19S Proteasomal Regulatory Particle Using Chemical Cross-linking and Probabilistic Modeling* , 2012, Molecular & Cellular Proteomics.

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

[26]  J. Reilly,et al.  Structural analysis of a prokaryotic ribosome using a novel amidinating cross-linker and mass spectrometry. , 2011, Journal of proteome research.

[27]  Andrea Sinz,et al.  Chemical cross-linking and mass spectrometry to map three-dimensional protein structures and protein-protein interactions. , 2006, Mass spectrometry reviews.

[28]  David Baker,et al.  Interactions of the Transmembrane Polymeric Rings of the Salmonella enterica Serovar Typhimurium Type III Secretion System , 2010, mBio.

[29]  Min Zhou,et al.  Mass spectrometry of membrane transporters reveals subunit stoichiometry and interactions , 2009, Nature Methods.

[30]  Albert J R Heck,et al.  High-resolution mass spectrometry of viral assemblies: Molecular composition and stability of dimorphic hepatitis B virus capsids , 2008, Proceedings of the National Academy of Sciences.

[31]  C. Robinson,et al.  Protein complexes in the gas phase: technology for structural genomics and proteomics. , 2007, Chemical reviews.

[32]  R. Aebersold,et al.  Joining Forces: Integrating Proteomics and Cross-linking with the Mass Spectrometry of Intact Complexes* , 2011, Molecular & Cellular Proteomics.

[33]  G. Montoya,et al.  Chaperonins: two rings for folding. , 2011, Trends in biochemical sciences.

[34]  R. Huber,et al.  Structure of 20S proteasome from yeast at 2.4Å resolution , 1997, Nature.

[35]  Sean R. Collins,et al.  Global landscape of protein complexes in the yeast Saccharomyces cerevisiae , 2006, Nature.

[36]  C. Robinson,et al.  Aspects of native proteins are retained in vacuum. , 2006, Current opinion in chemical biology.

[37]  T. Steitz,et al.  The complete atomic structure of the large ribosomal subunit at 2.4 A resolution. , 2000, Science.

[38]  Carol V. Robinson,et al.  Mass Spectrometry of Intact V-Type ATPases Reveals Bound Lipids and the Effects of Nucleotide Binding , 2011, Science.

[39]  Andreas Bracher,et al.  The molecular architecture of the eukaryotic chaperonin TRiC/CCT. , 2012, Structure.

[40]  Julie Grantham,et al.  The inter‐ring arrangement of the cytosolic chaperonin CCT , 2007, EMBO reports.

[41]  A. Heck.  Native mass spectrometry: a bridge between interactomics and structural biology , 2008, Nature Methods.

[42]  J. Bruce,et al.  Profiling the membrane proteome of Shewanella oneidensis MR-1 with new affinity labeling probes. , 2007, Journal of proteome research.

[43]  Hugh-George Patterton,et al.  Bioinformatics tools for the structural elucidation of multi-subunit protein complexes by mass spectrometric analysis of protein-protein cross-links , 2011, Briefings Bioinform..

[44]  K. Willison,et al.  Elucidation of the subunit orientation in CCT (chaperonin containing TCP1) from the subunit composition of CCT micro‐complexes , 1997, The EMBO journal.

[45]  Frank Alber,et al.  Integrating diverse data for structure determination of macromolecular assemblies. , 2008, Annual review of biochemistry.

[46]  Christoph H. Borchers,et al.  An Isotopically Coded CID-cleavable Biotinylated Cross-linker for Structural Proteomics* , 2010, Molecular & Cellular Proteomics.

[47]  Fabienne Beuron,et al.  The crystal structure of yeast CCT reveals intrinsic asymmetry of eukaryotic cytosolic chaperonins , 2011, The EMBO journal.

[48]  Ruedi Aebersold,et al.  Crosslinking-MS analysis reveals RNA polymerase I domain architecture and basis of rRNA cleavage , 2012, Nucleic acids research.

[49]  S. Jentsch,et al.  The Ubiquitin System in Health and Disease , 2009 .

[50]  Wah Chiu,et al.  4.0-Å resolution cryo-EM structure of the mammalian chaperonin TRiC/CCT reveals its unique subunit arrangement , 2010, Proceedings of the National Academy of Sciences.

[51]  R. Aebersold,et al.  Structural Probing of a Protein Phosphatase 2A Network by Chemical Cross-Linking and Mass Spectrometry , 2012, Science.

[52]  J. Bruce,et al.  Collisionally activated dissociation and electron capture dissociation of several mass spectrometry-identifiable chemical cross-linkers. , 2006, Analytical chemistry.

[53]  P. Wingfield,et al.  Subunit exchange rates in Hepatitis B virus capsids are geometry- and temperature-dependent. , 2010, Physical chemistry chemical physics : PCCP.

[54]  M. Dong,et al.  Identification of cross-linked peptides from complex samples , 2012, Nature Methods.

[55]  Malin M. Young,et al.  High throughput protein fold identification by using experimental constraints derived from intramolecular cross-links and mass spectrometry , 2000, Proc. Natl. Acad. Sci. USA.

[56]  Edith D. Wong,et al.  Saccharomyces Genome Database: the genomics resource of budding yeast , 2011, Nucleic Acids Res..

[57]  P. Bork,et al.  Proteome survey reveals modularity of the yeast cell machinery , 2006, Nature.

[58]  Arlo Z. Randall,et al.  Development of a Novel Cross-linking Strategy for Fast and Accurate Identification of Cross-linked Peptides of Protein Complexes* , 2010, Molecular & Cellular Proteomics.

[59]  F. Förster,et al.  The catalytic activity of Ubp6 enhances maturation of the proteasomal regulatory particle. , 2011, Molecular cell.

[60]  Chris G de Koster,et al.  Chemical cross-linking and mass spectrometry for protein structural modeling. , 2003, Journal of molecular biology.

[61]  P. Cramer,et al.  Structural Basis of Transcription: RNA Polymerase II at 2.8 Ångstrom Resolution , 2001, Science.

[62]  M. Gerstein,et al.  Defining the TRiC/CCT interactome links chaperonin function to stabilization of newly-made proteins with complex topologies , 2008, Nature Structural &Molecular Biology.

[63]  Florian Stengel,et al.  Dissecting heterogeneous molecular chaperone complexes using a mass spectrum deconvolution approach. , 2012, Chemistry & biology.

[64]  R. Huber,et al.  Crystal structure of the 20S proteasome from the archaeon T. acidophilum at 3.4 A resolution. , 1995, Science.

[65]  T. Earnest,et al.  From words to literature in structural proteomics , 2003, Nature.

[66]  R. Aebersold,et al.  Molecular architecture of the 26S proteasome holocomplex determined by an integrative approach , 2012, Proceedings of the National Academy of Sciences.

[67]  Edward P. Morris,et al.  Structural basis for the subunit assembly of the anaphase-promoting complex , 2011, Nature.

[68]  E. Conti,et al.  The archaeal exosome core is a hexameric ring structure with three catalytic subunits , 2005, Nature Structural &Molecular Biology.

[69]  P. Cramer,et al.  Structural biology of RNA polymerase III: mass spectrometry elucidates subcomplex architecture. , 2007, Structure.

[70]  Juri Rappsilber,et al.  Structural Analysis of Multiprotein Complexes by Cross-linking, Mass Spectrometry, and Database Searching*S , 2007, Molecular & Cellular Proteomics.

[71]  J. Rappsilber.  The beginning of a beautiful friendship: Cross-linking/mass spectrometry and modelling of proteins and multi-protein complexes , 2011, Journal of structural biology.

[72]  B. Alberts.  The Cell as a Collection of Protein Machines: Preparing the Next Generation of Molecular Biologists , 1998, Cell.

[73]  Lars Konermann,et al.  Hydrogen exchange mass spectrometry for studying protein structure and dynamics. , 2011, Chemical Society reviews.

[74]  Quansheng Liu,et al.  Reconstitution, Activities, and Structure of the Eukaryotic RNA Exosome , 2006, Cell.

[75]  Michael Levitt,et al.  Subunit order of eukaryotic TRiC/CCT chaperonin by cross-linking, mass spectrometry, and combinatorial homology modeling , 2012, Proceedings of the National Academy of Sciences.

[76]  R. Aebersold,et al.  Probing Native Protein Structures by Chemical Cross-linking, Mass Spectrometry, and Bioinformatics* , 2010, Molecular & Cellular Proteomics.

[77]  Andreas Bracher,et al.  Molecular chaperones in protein folding and proteostasis , 2011, Nature.