| Structural highlights
Disease
DRD5_HUMAN Disease susceptibility may be associated with variants affecting the gene represented in this entry.
Function
DRD5_HUMAN Dopamine receptor whose activity is mediated by G proteins which activate adenylyl cyclase.[1] C562_ECOLX Electron-transport protein of unknown function.
Publication Abstract from PubMed
The dopaminergic system, including five dopamine receptors (D1R to D5R), plays essential roles in the central nervous system (CNS); and ligands that activate dopamine receptors have been used to treat many neuropsychiatric disorders, including Parkinson's Disease (PD) and schizophrenia. Here, we report cryo-EM structures of all five subtypes of human dopamine receptors in complex with G protein and bound to the pan-agonist, rotigotine, which is used to treat PD and restless legs syndrome. The structures reveal the basis of rotigotine recognition in different dopamine receptors. Structural analysis together with functional assays illuminate determinants of ligand polypharmacology and selectivity. The structures also uncover the mechanisms of dopamine receptor activation, unique structural features among the five receptor subtypes, and the basis of G protein coupling specificity. Our work provides a comprehensive set of structural templates for the rational design of specific ligands to treat CNS diseases targeting the dopaminergic system.
Structural genomics of the human dopamine receptor system.,Xu P, Huang S, Krumm BE, Zhuang Y, Mao C, Zhang Y, Wang Y, Huang XP, Liu YF, He X, Li H, Yin W, Jiang Y, Zhang Y, Roth BL, Xu HE Cell Res. 2023 May 23. doi: 10.1038/s41422-023-00808-0. PMID:37221270[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Weinshank RL, Adham N, Macchi M, Olsen MA, Branchek TA, Hartig PR. Molecular cloning and characterization of a high affinity dopamine receptor (D1 beta) and its pseudogene. J Biol Chem. 1991 Nov 25;266(33):22427-35 PMID:1834671
- ↑ Xu P, Huang S, Krumm BE, Zhuang Y, Mao C, Zhang Y, Wang Y, Huang XP, Liu YF, He X, Li H, Yin W, Jiang Y, Zhang Y, Roth BL, Xu HE. Structural genomics of the human dopamine receptor system. Cell Res. 2023 May 23. PMID:37221270 doi:10.1038/s41422-023-00808-0
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