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Methods. 2015 Nov 1;89:54-63. doi: 10.1016/j.ymeth.2015.06.010. Epub 2015 Jun 12.

XL-MS: Protein cross-linking coupled with mass spectrometry.

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Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK. Electronic address:


With the continuing trend to study larger and more complex systems, the application of protein cross-linking coupled with mass spectrometry (XL-MS) provides a varied toolkit perfectly suited to achieve these goals. By freezing the transient interactions through the formation of covalent bonds, XL-MS provides a vital insight into both the structure and organization of proteins in a wide variety of conditions. This review covers some of the established methods that underpin the field alongside the more recent developments that hold promise to further realize its potential in new directions.


Cross-linking; Mass spectrometry; Proteomics; Quantitation; Structure; Systems biology; XL-MS

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