7ckz

Cryo-EM structure of Dopamine and LY3154207 bound dopamine receptor DRD1-Gs signaling complex

spinqualitylabelsall models 7ckz, resolution 3.10Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7ckz is a 5 chain structure with sequence from Homo sapiens and Lama glama. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.1Å Ligands: CLR, G4C, LDP Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Dopamine receptors, including D1- and D2-like receptors, are important therapeutic targets in a variety of neurological syndromes, as well as cardiovascular and kidney diseases. Here, we present five cryoelectron microscopy (cryo-EM) structures of the dopamine D1 receptor (DRD1) coupled to Gs heterotrimer in complex with three catechol-based agonists, a non-catechol agonist, and a positive allosteric modulator for endogenous dopamine. These structures revealed that a polar interaction network is essential for catecholamine-like agonist recognition, whereas specific motifs in the extended binding pocket were responsible for discriminating D1- from D2-like receptors. Moreover, allosteric binding at a distinct inner surface pocket improved the activity of DRD1 by stabilizing endogenous dopamine interaction at the orthosteric site. DRD1-Gs interface revealed key features that serve as determinants for G protein coupling. Together, our study provides a structural understanding of the ligand recognition, allosteric regulation, and G protein coupling mechanisms of DRD1. Ligand recognition and allosteric regulation of DRD1-Gs signaling complexes.,Xiao P, Yan W, Gou L, Zhong YN, Kong L, Wu C, Wen X, Yuan Y, Cao S, Qu C, Yang X, Yang CC, Xia A, Hu Z, Zhang Q, He YH, Zhang DL, Zhang C, Hou GH, Liu H, Zhu L, Fu P, Yang S, Rosenbaum DM, Sun JP, Du Y, Zhang L, Yu X, Shao Z Cell. 2021 Feb 18;184(4):943-956.e18. doi: 10.1016/j.cell.2021.01.028. Epub 2021 , Feb 10. PMID:33571432 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Antibody 3D structures Dopamine receptor 3D structures Transducin 3D structures

Proteopedia Page Contributors and Editors (what is this?)

OCA