Photoactivated SOPP3 enables APEX2-mediated proximity labeling with high spatio-temporal resolution in live cells

Proximity labeling (PL) is an emerging technology for probing protein interactome in living cells. Current PL technology, like using engineered peroxidases (APEX2, HRP), is widely employed, benefiting from their high temporal resolution. 1 , 2 However, cytotoxicity of exogenous H 2 O 2 , which is used to activate APEX2, largely limits its application. Meanwhile, PL methods employing biotin ligases, such as BioID, 3 BioID2, 4 TurboID, 5 give poor temporal resolution due to low catalytic activity and prolonged labeling time. An approach that could catalyze PL in living cells with high spatio-temporal resolution is still missing.