6H3E

Receptor-bound Ghrelin conformation

Summary for 6H3E

• Entry DOI: 10.2210/pdb6h3e/pdb
• NMR Information: BMRB: 34303
• Descriptor: Appetite-regulating hormone, octan-1-amine (2 entities in total)
• Functional Keywords: neuropeptide, acyl chain, growth hormone secretagogue receptor, gpcr, lipopeptide hormone, obesity, diabetes, addiction., hormone
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 2259.54

Authors

Ferre, G.,Damian, M.,M'Kadmi, C.,Saurel, O.,Czaplicki, G.,Demange, P.,Marie, J.,Fehrentz, J.A.,Baneres, J.L.,Milon, A. (deposition date: 2018-07-18, release date: 2019-07-24, Last modification date: 2024-10-23)

Primary citation

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, J.A.,Floquet, N.,Milon, A.,Baneres, J.L.
Structure and dynamics of G protein-coupled receptor-bound ghrelin reveal the critical role of the octanoyl chain.
Proc.Natl.Acad.Sci.USA, 116:17525-17530, 2019

PubMed 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 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.

PubMed: 31416915
DOI: 10.1073/pnas.1905105116

Experimental method

SOLUTION NMR