7jvq

Cryo-EM structure of apomorphine-bound dopamine receptor 1 in complex with Gs protein

spinqualitylabelsall models 7jvq, resolution 3.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7jvq 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: CLR, OR9, PLM Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function DRD1_HUMAN Dopamine receptor whose activity is mediated by G proteins which activate adenylyl cyclase. Publication Abstract from PubMed The D1- and D2-dopamine receptors (D1R and D2R), which signal through G(s) and G(i), respectively, represent the principal stimulatory and inhibitory dopamine receptors in the central nervous system. D1R and D2R also represent the main therapeutic targets for Parkinson's disease, schizophrenia, and many other neuropsychiatric disorders, and insight into their signaling is essential for understanding both therapeutic and side effects of dopaminergic drugs. Here, we report four cryoelectron microscopy (cryo-EM) structures of D1R-G(s) and D2R-G(i) signaling complexes with selective and non-selective dopamine agonists, including two currently used anti-Parkinson's disease drugs, apomorphine and bromocriptine. These structures, together with mutagenesis studies, reveal the conserved binding mode of dopamine agonists, the unique pocket topology underlying ligand selectivity, the conformational changes in receptor activation, and potential structural determinants for G protein-coupling selectivity. These results provide both a molecular understanding of dopamine signaling and multiple structural templates for drug design targeting the dopaminergic system. Structural insights into the human D1 and D2 dopamine receptor signaling complexes.,Zhuang Y, Xu P, Mao C, Wang L, Krumm B, Zhou XE, Huang S, Liu H, Cheng X, Huang XP, Shen DD, Xu T, Liu YF, Wang Y, Guo J, Jiang Y, Jiang H, Melcher K, Roth BL, Zhang Y, Zhang C, Xu HE Cell. 2021 Feb 18;184(4):931-942.e18. doi: 10.1016/j.cell.2021.01.027. Epub 2021 , Feb 10. PMID:33571431 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Dopamine receptor 3D structures Transducin 3D structures

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