Conformational fingerprinting of allosteric modulators in metabotropic glutamate receptor 2.

ABSTRACT: Activation of G protein-coupled receptors (GPCRs) is an allosteric process. It involves conformational coupling between the orthosteric ligand binding site and the G protein binding site. Factors that bind at non-cognate ligand binding sites to alter the allosteric activation process are classified as allosteric modulators and represent a promising class of therapeutics with distinct modes of binding and action. For many receptors, how modulation of signaling is represented at the structural level is unclear. Here, we developed fluorescence resonance energy transfer (FRET) sensors to quantify receptor modulation at each of the three structural domains of metabotropic glutamate receptor 2 (mGluR2). We identified the conformational fingerprint for several allosteric modulators in live cells.

SUBMITTER: Liauw BW 

PROVIDER: S-EPMC9299836 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature