National Natural Science Foundation of China (NSFC)
31770796
China
Citation
Journal: Nat Commun / Year: 2021 Title: Molecular recognition of an acyl-peptide hormone and activation of ghrelin receptor. Authors: Yue Wang / Shimeng Guo / Youwen Zhuang / Ying Yun / Peiyu Xu / Xinheng He / Jia Guo / Wanchao Yin / H Eric Xu / Xin Xie / Yi Jiang / Abstract: 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.
Mass: 41855.578 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Spodoptera frugiperda (fall armyworm)
#6: Protein
Solublecytochromeb562
Mass: 74282.609 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: cybC / Production host: Spodoptera frugiperda (fall armyworm)
-
Guanine nucleotide-binding protein ... , 2 types, 2 molecules BG
Mass: 3252.726 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: GHRL, MTLRP, UNQ524/PRO1066 / Production host: Homo sapiens (human) / References: UniProt: Q9UBU3
#5: Antibody
NB35
Mass: 15343.019 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Lama glama (llama) / Production host: Escherichia coli (E. coli)
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