Photo-lysine, a new lysine-based photo-reactive amino acid, captures proteins that bind lysine post-translational modifications.
Photo-lysine is designed and synthesized by incorporating a photo-cross-linker (diazirine) into the side chain of natural lysine. Photo-lysine, which is readily incorporated into proteins by native mammalian translation machinery, can be used to capture and identify proteins that recognize lysine post-translational modifications (PTMs), including 'readers' and 'erasers' of histone modifications. Photo-lysine can be incorporated into MDH2 and mediate photo-cross-linking to fix protein-protein interactions in cells. UV irradiation of cells in the presence of photo-lysine induced robust cross-linking of HSP90β and HSP60. Photo-lysine has higher efficiency than photo-leucine for photo-cross-linking of the two chaperone proteins. Photo-lysine enables capture of the heterodimer of proteins Ku70 and Ku80 within a protein complex. Photo-lysine enables identification of histone- and chromatin-binding proteins[1].
[1]. Yang T, et al. Photo-lysine captures proteins that bind lysine post-translational modifications. Nat Chem Biol. 2016 Feb;12(2):70-2.