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

Nat Methods. 2015 Dec;12(12):1185-90. doi: 10.1038/nmeth.3631. Epub 2015 Oct 26.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Animals
  • Chaperonin Containing TCP-1 / chemistry*
  • Cross-Linking Reagents / chemistry*
  • Data Interpretation, Statistical
  • Databases, Protein
  • Luciferases, Firefly / chemistry*
  • Mass Spectrometry / methods*
  • Models, Molecular
  • Multiprotein Complexes / chemistry*
  • Protein Conformation
  • Software*


  • Cross-Linking Reagents
  • Multiprotein Complexes
  • Luciferases, Firefly
  • Chaperonin Containing TCP-1