6h3e

Receptor-bound Ghrelin conformation

spinqualitylabelsall models 6h3e Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6h3e is a 1 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Solution NMR, 10 models Ligands: FKZ, NH2 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function GHRL_HUMAN Ghrelin is the ligand for growth hormone secretagogue receptor type 1 (GHSR). Induces the release of growth hormone from the pituitary. Has an appetite-stimulating effect, induces adiposity and stimulates gastric acid secretion. Involved in growth regulation. Obestatin may be the ligand for GPR39. May have an appetite-reducing effect resulting in decreased food intake. May reduce gastric emptying activity and jejunal motility (By similarity). Publication Abstract from PubMed 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 improving our mechanistic understanding of the complex conformational space explored by a natural peptide agonist when binding to its GPCR. Such information should also facilitate the design of new ghrelin receptor-selective drugs. Structure and dynamics of G protein-coupled receptor-bound ghrelin reveal the critical role of the octanoyl chain.,Ferre G, Louet M, Saurel O, Delort B, Czaplicki G, M'Kadmi C, Damian M, Renault P, Cantel S, Gavara L, Demange P, Marie J, Fehrentz JA, Floquet N, Milon A, Baneres JL Proc Natl Acad Sci U S A. 2019 Aug 15. pii: 1905105116. doi:, 10.1073/pnas.1905105116. PMID:31416915 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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