The site-specific installation of light-activable crosslinker unnatural amino acids offers a powerful approach to trap transient protein-protein interactions both and . Herein, we engineer a bromodomain to introduce 4-benzoyl-L-phenylalanine (BzF) using amber suppressor mutagenesis without compromising its ability to recognize the acetylated histone proteins. We demonstrate the high crosslinking efficiency of the engineered reader towards the interacting partners and its suitability for profiling the transient bromodomain interactome.
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