7F8V

Cryo-EM structure of the cholecystokinin receptor CCKBR in complex with gastrin-17 and Gi

Summary for 7F8V

• Entry DOI: 10.2210/pdb7f8v/pdb
• EMDB information: 31493 31494
• Descriptor: Guanine nucleotide-binding protein G(i) subunit alpha-2, Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2, ... (5 entities in total)
• Functional Keywords: g protein-coulped receptor, cholecystokinin receptor cckbr, gastrin-17, structural protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 5
• Total formula weight: 139731.50

Authors

Zhang, X.,He, C.,Wang, M.,Zhou, Q.,Yang, D.,Zhu, Y.,Wu, B.,Zhao, Q. (deposition date: 2021-07-02, release date: 2021-10-13, Last modification date: 2022-02-16)

Primary citation

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, H.E.,Zhao, S.,Wang, M.W.,Wu, B.,Zhao, Q.
Structures of the human cholecystokinin receptors bound to agonists and antagonists.
Nat.Chem.Biol., 17:1230-1237, 2021

PubMed Abstract: Cholecystokinin receptors, CCKR and CCKR, 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 CCKR in complex with different ligands, including one peptide agonist and two small-molecule antagonists, as well as two cryo-electron microscopy structures of CCKR-gastrin in complex with G and G, 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.

PubMed: 34556863
DOI: 10.1038/s41589-021-00866-8

Experimental method

ELECTRON MICROSCOPY (3.3 Å)