Yang, T. et al. Nat. Chem. Biol. doi:10.1038/nchembio.1990 (21 December 2015).
Protein post-translational modifications (PTMs), such as those found on lysine residues in histones, have important jobs in regulating protein interactions. These interactions are challenging to capture, however, as they are often weak and the PTMs themselves are present at low levels. Yang et al. describe an approach for capturing interactions dependent on lysine PTMs by utilizing photo–cross-linking. They designed a photo-reactive lysine that, when provided as the exclusive lysine source in cell culture, is incorporated in place of the native lysine and undergoes modification after translation. The photo-lysine residue, which contains a diazirine moiety, will form a covalent bond with binding proteins in close proximity upon photo–cross-linking. Such binding partners then can be identified using proteomics methods. The tool enabled Yang et al. to identify histone modification readers and erasers in live cells.