title: Probing native protein structures by chemical cross-linking, mass spectrometry, and bioinformatics.
abstract: Chemical cross-linking of reactive groups in native proteins and protein complexes in combination with the identification of cross-linked sites by mass spectrometry has been in use for more than a decade. Recent advances in instrumentation, cross-linking protocols, and analysis software have led to a renewed interest in this technique, which promises to provide important information about native protein structure and the topology of protein complexes. In this article, we discuss the critical steps of chemical cross-linking and its implications for (structural) biology: reagent design and cross-linking protocols, separation and mass spectrometric analysis of cross-linked samples, dedicated software for data analysis, and the use of cross-linking data for computational modeling. Finally, the impact of protein cross-linking on various biological disciplines is highlighted.
authors.affiliation: Institute of Molecular Systems Biology, Eidgenössiche Technische Hochschule (ETH) Zurich, Zurich, Switzerland.
authors.forename: Alexander
authors.initials: A
authors.lastname: Leitner
authors.forename: Thomas
authors.initials: T
authors.lastname: Walzthoeni
authors.forename: Abdullah
authors.initials: A
authors.lastname: Kahraman
authors.forename: Franz
authors.initials: F
authors.lastname: Herzog
authors.forename: Oliver
authors.initials: O
authors.lastname: Rinner
authors.forename: Martin
authors.initials: M
authors.lastname: Beck
authors.forename: Ruedi
authors.initials: R
authors.lastname: Aebersold
mesh_terms: D019295:Computational Biology / Q000379:methods*; D003432:Cross-Linking Reagents / Q000737:chemistry* / Q000494:pharmacology; D013058:Mass Spectrometry / Q000379:methods*; D008958:Models, Molecular; D011487:Protein Conformation / Q000187:drug effects; D011506:Proteins / Q000737:chemistry*
chemical_list: D003432:Cross-Linking Reagents; D011506:Proteins