Structure and dynamics of G protein-coupled receptor-bound ghrelin reveal the critical role of the octanoyl chain.

ABSTRACT: Ghrelin plays a central role in controlling major biological processes. As for other G protein-coupled receptor (GPCR) peptide agonists, the structure and dynamics of ghrelin bound to its receptor remain obscure. Using a combination of solution-state NMR and molecular modeling, we demonstrate that binding to the growth hormone secretagogue receptor is accompanied by a conformational change in ghrelin that structures its central region, involving the formation of a well-defined hydrophobic core. By comparing its acylated and nonacylated forms, we conclude that the ghrelin octanoyl chain is essential to form the hydrophobic core and promote access of ghrelin to the receptor ligand-binding pocket. The combination of coarse-grained molecular dynamics studies and NMR should prove useful in impr

SUBMITTER: Ferre G 

PROVIDER: S-EPMC6717258 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature