Summary for 8IA7
| Entry DOI | 10.2210/pdb8ia7/pdb |
| EMDB information | 35297 |
| Descriptor | Gastrin/cholecystokinin type B receptor, 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, ... (6 entities in total) |
| Functional Keywords | brain gut peptide receptor class a g-protein-coupled receptor, neuropeptide |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 6 |
| Total formula weight | 165309.62 |
| Authors | |
| Primary citation | Ding, Y.,Zhang, H.,Liao, Y.Y.,Chen, L.N.,Ji, S.Y.,Qin, J.,Mao, C.,Shen, D.D.,Lin, L.,Wang, H.,Zhang, Y.,Li, X.M. Structural insights into human brain-gut peptide cholecystokinin receptors. Cell Discov, 8:55-55, 2022 Cited by PubMed Abstract: The intestinal hormone and neuromodulator cholecystokinin (CCK) receptors CCK1R and CCK2R act as a signaling hub in brain-gut axis, mediating digestion, emotion, and memory regulation. CCK receptors exhibit distinct preferences for ligands in different posttranslational modification (PTM) states. CCK1R couples to G and G, whereas CCK2R primarily couples to G. Here we report the cryo-electron microscopy (cryo-EM) structures of CCK1R-G signaling complexes liganded either by sulfated cholecystokinin octapeptide (CCK-8) or a CCK1R-selective small-molecule SR146131, and CCK2R-G complexes stabilized by either sulfated CCK-8 or a CCK2R-selective ligand gastrin-17. Our structures reveal a location-conserved yet charge-distinct pocket discriminating the effects of ligand PTM states on receptor subtype preference, the unique pocket topology underlying selectivity of SR146131 and gastrin-17, the conformational changes in receptor activation, and key residues contributing to G protein subtype specificity, providing multiple structural templates for drug design targeting the brain-gut axis. PubMed: 35672283DOI: 10.1038/s41421-022-00420-3 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.1 Å) |
Structure validation
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