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xTract: software for characterizing conformational changes of protein complexes by quantitative cross-linking mass spectrometry.

Type Information
Nr 52 (Research article)
Authors Walzthoeni, Thomas; Joachimiak, Lukasz; Rosenberger, George; Röst, Hannes; Malmström, Lars; Leitner, Alexander; Frydman, Judith; Aebersold, Ruedi
Title xTract: software for characterizing conformational changes of protein complexes by quantitative cross-linking mass spectrometry.
Journal Nat Methods (2015) 12(12) 1185-90
DOI 10.1038/nmeth.3631
Citations 101 citations (journal impact: 25.95)
Abstract Chemical cross-linking in combination with mass spectrometry generates distance restraints of amino acid pairs in close proximity on the surface of native proteins and protein complexes. In this study we used quantitative mass spectrometry and chemical cross-linking to quantify differences in cross-linked peptides obtained from complexes in spatially discrete states. We describe a generic computational pipeline for quantitative cross-linking mass spectrometry consisting of modules for quantitative data extraction and statistical assessment of the obtained results. We used the method to detect conformational changes in two model systems firefly luciferase and the bovine TRiC complex. Our method discovers and explains the structural heterogeneity of protein complexes using only sparse structural information.