Abstract
Genetic code expansion technology has been widely applied to control protein activity and biological systems by taking advantage of an amber stop codon suppressor tRNA and orthogonal aminoacyl-tRNA synthetase pair. With this chemical biology approach, Maltan et al. incorporated photocrosslinking unnatural amino acids (UAAs) into the transmembrane domains of ORAI1 to enable UV light-inducible calcium influx across the plasma membrane, mechanistic interrogation of the calcium release-activated calcium (CRAC) channel at the single amino acid level, and remote control of downstream calcium-modulated signaling in mammalian cells.