6H3E

Receptor-bound Ghrelin conformation

6H3E の概要

• エントリーDOI: 10.2210/pdb6h3e/pdb
• NMR情報: BMRB: 34303
• 分子名称: Appetite-regulating hormone, octan-1-amine (2 entities in total)
• 機能のキーワード: neuropeptide, acyl chain, growth hormone secretagogue receptor, gpcr, lipopeptide hormone, obesity, diabetes, addiction., hormone
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 2259.54

構造登録者

Ferre, G.,Damian, M.,M'Kadmi, C.,Saurel, O.,Czaplicki, G.,Demange, P.,Marie, J.,Fehrentz, J.A.,Baneres, J.L.,Milon, A. (登録日: 2018-07-18, 公開日: 2019-07-24, 最終更新日: 2024-10-23)

主引用文献

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

実験手法

SOLUTION NMR