GPCR-G protein selectivity – a unified meta-analysis

Abstract

Two-thirds of human hormones and one-third of clinical drugs act on membrane receptors that couple to G proteins to achieve appropriate functional responses. While G protein transducers from literature are annotated in the Guide to Pharmacology database, two recent large-scale datasets now expand the receptor-G protein ‘couplome’. However, these three datasets differ in scope and reported G protein couplings giving different coverage and conclusions on GPCR-G protein signaling. Here, we report a meta-analysis unifying GPCR-G protein coupling, by standardized normalization and consensus support, into a common coupling map. This unravels novel consensus couplings for receptors supported by two independent sources and insights on coupling selectivity of GPCRs and classification of co-coupling G proteins. The coupling protocol, map and selectivity resources will promote advances in receptor research and cellular signaling towards the exploitation of G protein signaling specificity in design of safer drugs.