Genetically encoded photocrosslinkers for identifying and mapping protein-protein interactions in living cells.

Protein-protein interactions (PPIs) play pivotal roles in regulation of many biological processes. Conventional methods are capable of investigating stable and strong interactions within protein complexes, but remain difficult for studying dynamic, transient, and weak PPIs. Herein we review photo-affinity unnatural amino acids that can be site-specifically incorporated into a protein of interest to covalently trap noncovalent PPIs under living conditions. A newly developed cleavable photocrosslinker from our group will also be introduced, which facilitated the prey-bait separation for better enrichment and identification of photocrosslinked PPI complexes.