Conformational dynamics of a G protein-coupled receptor helix 8 in lipid membranes.

ABSTRACT: G protein-coupled receptors (GPCRs) are the largest and pharmaceutically most important class of membrane proteins encoded in the human genome, characterized by a seven-transmembrane helix architecture and a C-terminal amphipathic helix 8 (H8). In a minority of GPCR structures solved to date, H8 either is absent or adopts an unusual conformation. The controversial existence of H8 of the class A GPCR neurotensin receptor 1 (NTS1) has been examined here for the nonthermostabilized receptor in a functionally supporting membrane environment using electron paramagnetic resonance, molecular dynamics simulations, and circular dichroism. Lipid-protein interactions with phosphatidylserine and phosphatidylethanolamine lipids, in particular, stabilize the residues 374 to 390 of NTS1 into forming a he

SUBMITTER: Dijkman PM 

PROVIDER: S-EPMC7428336 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature