Quantitative interactome analysis with chemical cross- linking and mass spectrometry

Structural plasticity and dynamic protein-protein interactions are critical determinants of protein function within living sys-tems. Quantitative chemical cross-linking with mass spec-trometry (qXL-MS) is an emerging technology able to provide information on changes in protein conformations and in-teractions. Importantly, qXL-MS is applicable to complex bio-logical systems, including living cells and tissues, thereby providing insights into proteins within their native environ -ments. Here, we present an overview of recent technological developments and applications involving qXL-MS, including design and synthesis of isotope-labeled cross-linkers, devel-opment of new liquid chromatography-MS methodologies, and computational developments enabling interpretation of the data.