受体
N端
细胞外
跨膜结构域
肽
C端
跨膜蛋白
G蛋白偶联受体
化学
细胞生物学
肽序列
生物
生物化学
激素
氨基酸
基因
作者
Fuqiang Zhao,Chao Zhang,Qingtong Zhou,Kaini Hang,Xinyu Zou,Yan Chen,Fan Wu,Qidi Rao,Antao Dai,Wanchao Yin,Dandan Shen,Yan Zhang,Tian Xia,Raymond C. Stevens,H. Y. Xu,Dehua Yang,Lihua Zhao,Mingwei Wang
出处
期刊:eLife
[eLife Sciences Publications, Ltd.]
日期:2021-07-13
卷期号:10
被引量:32
摘要
Glucose-dependent insulinotropic polypeptide (GIP) is a peptide hormone that exerts crucial metabolic functions by binding and activating its cognate receptor, GIPR. As an important therapeutic target, GIPR has been subjected to intensive structural studies without success. Here, we report the cryo-EM structure of the human GIPR in complex with GIP and a Gs heterotrimer at a global resolution of 2.9 Å. GIP adopts a single straight helix with its N terminus dipped into the receptor transmembrane domain (TMD), while the C terminus is closely associated with the extracellular domain and extracellular loop 1. GIPR employs conserved residues in the lower half of the TMD pocket to recognize the common segments shared by GIP homologous peptides, while uses non-conserved residues in the upper half of the TMD pocket to interact with residues specific for GIP. These results provide a structural framework of hormone recognition and GIPR activation.
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