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-Structure paper
タイトル | Molecular recognition of an acyl-peptide hormone and activation of ghrelin receptor. |
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ジャーナル・号・ページ | Nat Commun, Vol. 12, Issue 1, Page 5064, Year 2021 |
掲載日 | 2021年8月20日 |
著者 | Yue Wang / Shimeng Guo / Youwen Zhuang / Ying Yun / Peiyu Xu / Xinheng He / Jia Guo / Wanchao Yin / H Eric Xu / Xin Xie / Yi Jiang / |
PubMed 要旨 | Ghrelin, also called "the hunger hormone", is a gastric peptide hormone that regulates food intake, body weight, as well as taste sensation, reward, cognition, learning and memory. One unique feature ...Ghrelin, also called "the hunger hormone", is a gastric peptide hormone that regulates food intake, body weight, as well as taste sensation, reward, cognition, learning and memory. One unique feature of ghrelin is its acylation, primarily with an octanoic acid, which is essential for its binding and activation of the ghrelin receptor, a G protein-coupled receptor. The multifaceted roles of ghrelin make ghrelin receptor a highly attractive drug target for growth retardation, obesity, and metabolic disorders. Here we present two cryo-electron microscopy structures of G-coupled ghrelin receptor bound to ghrelin and a synthetic agonist, GHRP-6. Analysis of these two structures reveals a unique binding pocket for the octanoyl group, which guides the correct positioning of the peptide to initiate the receptor activation. Together with mutational and functional data, our structures define the rules for recognition of the acylated peptide hormone and activation of ghrelin receptor, and provide structural templates to facilitate drug design targeting ghrelin receptor. |
リンク | Nat Commun / PubMed:34417468 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 2.9 - 3.2 Å |
構造データ | EMDB-31500, PDB-7f9y: EMDB-31501, PDB-7f9z: |
化合物 | ChemComp-OCA: ChemComp-CLR: |
由来 |
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キーワード | MEMBRANE PROTEIN / ghrelin / GPCR / Gq / GHRP-6 |