Science 367, 1091–1097 (2020)

Existing spatial proximity proteomic methods such as APEX utilize enzymes that modify amino acid residues in neighboring proteins within a cellular compartment or microenvironment. However, these approaches are not amenable to revealing short-range interactions with temporal control. Geri et al. devised a light-inducible spatial proximity system, μMap, which uses blue light to excite an iridium-based photocatalyst to enable labeling of neighboring proximal proteins within a 1–10 nm radius. Blue-light exposure excites the catalyst conjugated to an antibody, which recognizes a target of interest to activate a biotinylated diazirine probe that modifies neighboring proteins, which can be identified through LC–MS analysis. The level of biotinylation correlates with the duration of blue-light exposure. The authors performed μMapping on programmed-death ligand 1 (PD-L1) in B cells, identifying CD30 and CD300A as potential new interactors. Finally, μMapping enabled trans-labeling of proteins on T cells during immunosynapse formation, confirming the utility of μMapping to detect protein interactions on the cell surface with close proximity and high precision.