7xov

Structural insights into human brain gut peptide cholecystokinin receptors

spinqualitylabelsall models 7xov, resolution 3.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7xov is a 5 chain structure with sequence from Homo sapiens and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3Å Ligands: IA1 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT 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 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(s) and G(q), whereas CCK2R primarily couples to G(q). Here we report the cryo-electron microscopy (cryo-EM) structures of CCK1R-G(s) signaling complexes liganded either by sulfated cholecystokinin octapeptide (CCK-8) or a CCK1R-selective small-molecule SR146131, and CCK2R-G(q) 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. Structural insights into human brain-gut peptide cholecystokinin receptors.,Ding Y, Zhang H, Liao YY, Chen LN, Ji SY, Qin J, Mao C, Shen DD, Lin L, Wang H, Zhang Y, Li XM Cell Discov. 2022 Jun 7;8(1):55. doi: 10.1038/s41421-022-00420-3. PMID:35672283 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Transducin 3D structures

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