High-mass MALDI-MS unravels ligand-mediated G protein-coupling selectivity to GPCRs.

ABSTRACT: G protein-coupled receptors (GPCRs) are important pharmaceutical targets for the treatment of a broad spectrum of diseases. Although there are structures of GPCRs in their active conformation with bound ligands and G proteins, the detailed molecular interplay between the receptors and their signaling partners remains challenging to decipher. To address this, we developed a high-sensitivity, high-throughput matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) method to interrogate the first stage of signal transduction. GPCR-G protein complex formation is detected as a proxy for the effect of ligands on GPCR conformation and on coupling selectivity. Over 70 ligand-GPCR-partner protein combinations were studied using as little as 1.25 pmol protein per sample. We determine

SUBMITTER: Wu N 

PROVIDER: S-EPMC8346855 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature