Kicking down the ladder:adding cleavable features to genetically encoded photocrosslinkers

Protein-protein interactions(PPIs)play vital roles in biological processes.However,the discovery of transient and biologically relevant PPIs remain a formidable challenge using conventional strategies such as co-immunoprecipitation(CoIP),yeast two hybrids(Y2H)and Forster resonance energy transfer(FRET)[1].Genetically encoded photocrosslinkers have recently emerged as a powerful approach for probing intracellular PPIs with the capability for in situ studies,low perturbation to cells as well as the wide generality.This facile strategy also demonstrated an advantage of high spatiotemporal resolution,which offers a robust capture strategy for the discovery of transient and/or weak PPIs with lowered false-positive backgrounds[2].