Structural insights into positive and negative allosteric regulation of a G protein-coupled receptor through protein-lipid interactions.

ABSTRACT: Lipids are becoming known as essential allosteric modulators of G protein-coupled receptor (GPCRs). However, how they exert their effects on GPCR conformation at the atomic level is still unclear. In light of recent experimental data, we have performed several long-timescale molecular dynamics (MD) simulations, totalling 24 μs, to rigorously map allosteric modulation and conformational changes in the β₂ adrenergic receptor (β2AR) that occur as a result of interactions with three different phospholipids. In particular, we identify different sequential mechanisms behind receptor activation and deactivation, respectively, mediated by specific lipid interactions with key receptor regions. We show that net negatively charged lipids stabilize an active-like state of β2AR that is able

SUBMITTER: Bruzzese A 

PROVIDER: S-EPMC5849739 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature