Anionic Phospholipids Control Mechanisms of GPCR-G Protein Recognition.

ABSTRACT: G protein-coupled receptors (GPCRs) are embedded in phospholipids that strongly influence drug-stimulated signaling. Anionic lipids are particularly important for GPCR signaling complex formation, but a mechanism for this role is not understood. Using NMR spectroscopy, we visualized the impact of anionic lipids on the function-related conformational equilibria of the human A _2A adenosine receptor (A _2A AR) in bilayers containing defined mixtures of zwitterionic and anionic phospholipids. Anionic lipids primed the receptor to form complexes with G proteins through a conformational selection process. Without anionic lipids, signaling complex formation proceeded through a less favorable induced fit mechanism. In computational models, anionic lipids mimicked interactions

SUBMITTER: Thakur N 

PROVIDER: S-EPMC9882065 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature