title: Mass spectrometry supported determination of protein complex structure.
abstract: 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.
authors.affiliation: Department of Biology, Institute of Molecular Systems Biology, ETH Zurich, Wolfgang-Pauli-Str. 16, 8093 Zurich, Switzerland.
authors.forename: Thomas
authors.initials: T
authors.lastname: Walzthoeni
authors.forename: Alexander
authors.initials: A
authors.lastname: Leitner
authors.forename: Florian
authors.initials: F
authors.lastname: Stengel
authors.forename: Ruedi
authors.initials: R
authors.lastname: Aebersold
mesh_terms: D000818:Animals; D018833:Chaperonins / Q000737:chemistry; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods*; D008958:Models, Molecular; D046912:Multiprotein Complexes / Q000737:chemistry*; D046988:Proteasome Endopeptidase Complex / Q000737:chemistry; D011487:Protein Conformation; D055503:Protein Multimerization; D021122:Protein Subunits / Q000737:chemistry
chemical_list: D046912:Multiprotein Complexes; D021122:Protein Subunits; D046988:Proteasome Endopeptidase Complex; C061553:ATP dependent 26S protease; D018833:Chaperonins