7x2d

Cryo-EM structure of the tavapadon-bound D1 dopamine receptor and mini-Gs complex

spinqualitylabelsall models 7x2d, resolution 3.30Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7x2d 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 3.3Å Ligands: 86W, CLR Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Dopamine receptors are widely distributed in the central nervous system and are important therapeutic targets for treatment of various psychiatric and neurological diseases. Here, we report three cryo-electron microscopy structures of the D1 dopamine receptor (D1R)-Gs complex bound to two agonists, fenoldopam and tavapadon, and a positive allosteric modulator LY3154207. The structure reveals unusual binding of two fenoldopam molecules, one to the orthosteric binding pocket (OBP) and the other to the extended binding pocket (EBP). In contrast, one elongated tavapadon molecule binds to D1R, extending from OBP to EBP. Moreover, LY3154207 stabilizes the second intracellular loop of D1R in an alpha helical conformation to efficiently engage the G protein. Through a combination of biochemical, biophysical and cellular assays, we further show that the broad conformation stabilized by two fenoldopam molecules and interaction between TM5 and the agonist are important for biased signaling of D1R. Ligand recognition and biased agonism of the D1 dopamine receptor.,Teng X, Chen S, Nie Y, Xiao P, Yu X, Shao Z, Zheng S Nat Commun. 2022 Jun 8;13(1):3186. doi: 10.1038/s41467-022-30929-w. PMID:35676276 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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