| Literature DB >> 34556863 |
Xuefeng Zhang1,2, Chenglin He3, Mu Wang1,2,4, Qingtong Zhou5,6, Dehua Yang1,2,7, Ya Zhu1, Wenbo Feng3, Hui Zhang1,2, Antao Dai7, Xiaojing Chu1, Jia Wang7, Zhenlin Yang1, Yi Jiang1, Ulrich Sensfuss8, Qiuxiang Tan1, Shuo Han1, Steffen Reedtz-Runge8, H Eric Xu1,2, Suwen Zhao9,10, Ming-Wei Wang11,12,13,14,15,16, Beili Wu17,18,19,20, Qiang Zhao21,22,23,24.
Abstract
Cholecystokinin receptors, CCKAR and CCKBR, are important neurointestinal peptide hormone receptors and play a vital role in food intake and appetite regulation. Here, we report three crystal structures of the human CCKAR in complex with different ligands, including one peptide agonist and two small-molecule antagonists, as well as two cryo-electron microscopy structures of CCKBR-gastrin in complex with Gi2 and Gq, respectively. These structures reveal the recognition pattern of different ligand types and the molecular basis of peptide selectivity in the cholecystokinin receptor family. By comparing receptor structures in different conformational states, a stepwise activation process of cholecystokinin receptors is proposed. Combined with pharmacological data, our results provide atomic details for differential ligand recognition and receptor activation mechanisms. These insights will facilitate the discovery of potential therapeutics targeting cholecystokinin receptors.Entities:
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Year: 2021 PMID： 34556863 DOI： 10.1038/s41589-021-00866-8
Source DB: PubMed Journal: Nat Chem Biol ISSN： 1552-4450 Impact factor: 15.040