μMap-uAA: Photocatalytic proximity labeling targeted with single-residue precision

Abstract

Mapping protein microenvironments with residue-level precision in living cells remains challenging. We report Map-uAA, a genetically encoded proximity labeling platform that uses unnatural amino acid incorporation to install a tetrazine-quenched iridium photocatalyst at user-defined protein sites through click chemistry. Photocatalysis is activated by covalent attachment to the incorporated uAA, enabling localized catalytic labeling of proximal biomolecules. Applied to membrane receptors, Map-uAA captures domain- and time-dependent GPCR interaction networks with residue-level spatial precision.