Solid-state NMR and molecular dynamics characterization of cannabinoid receptor-1 (CB1) helix 7 conformational plasticity in model membranes.

ABSTRACT: Little direct information is available regarding the influence of membrane environment on transmembrane (TM) G-protein-coupled receptor (GPCR) conformation and dynamics. The human CB1 cannabinoid receptor (hCB1) is a prominent GPCR pharmacotherapeutic target in which helix 7 appears critical to ligand recognition. We have chemically synthesized a hCB1 peptide corresponding to a segment of TM helix 7 and the entire contiguous helix 8 domain (fourth cytoplasmic loop) and reconstituted it in defined phospholipid-bilayer model membranes. Using an NMR-based strategy combined with molecular dynamics simulations, we provide the first direct experimental description of the orientation of hCB1 helix 7 in phospholipid membranes of varying thickness and the mechanism by which helix-7 conformation adj

SUBMITTER: Tiburu EK 

PROVIDER: S-EPMC3712639 | biostudies-literature | 2009 May

REPOSITORIES: biostudies-literature