| Structural highlights
Function
[CCKAR_HUMAN] Receptor for cholecystokinin. Mediates pancreatic growth and enzyme secretion, smooth muscle contraction of the gall bladder and stomach. Has a 1000-fold higher affinity for CCK rather than for gastrin. It modulates feeding and dopamine-induced behavior in the central and peripheral nervous system. This receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system.
Publication Abstract from PubMed
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.
Structures of the human cholecystokinin receptors bound to agonists and antagonists.,Zhang X, He C, Wang M, Zhou Q, Yang D, Zhu Y, Feng W, Zhang H, Dai A, Chu X, Wang J, Yang Z, Jiang Y, Sensfuss U, Tan Q, Han S, Reedtz-Runge S, Xu HE, Zhao S, Wang MW, Wu B, Zhao Q Nat Chem Biol. 2021 Sep 23. pii: 10.1038/s41589-021-00866-8. doi:, 10.1038/s41589-021-00866-8. PMID:34556863[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Zhang X, He C, Wang M, Zhou Q, Yang D, Zhu Y, Feng W, Zhang H, Dai A, Chu X, Wang J, Yang Z, Jiang Y, Sensfuss U, Tan Q, Han S, Reedtz-Runge S, Xu HE, Zhao S, Wang MW, Wu B, Zhao Q. Structures of the human cholecystokinin receptors bound to agonists and antagonists. Nat Chem Biol. 2021 Sep 23. pii: 10.1038/s41589-021-00866-8. doi:, 10.1038/s41589-021-00866-8. PMID:34556863 doi:http://dx.doi.org/10.1038/s41589-021-00866-8
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