Structural highlights
Disease
[DRD2_HUMAN] Myoclonic dystonia 11. The gene represented in this entry may be involved in disease pathogenesis. DRD2 mutations in myoclonic dystonia patients are rare, and their contribution to disease phenotype is unclear (PubMed:10716258).
Function
[DRD2_HUMAN] Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase (By similarity).[1] [2]
Publication Abstract from PubMed
Dopamine is a neurotransmitter that has been implicated in processes as diverse as reward, addiction, control of coordinated movement, metabolism and hormonal secretion. Correspondingly, dysregulation of the dopaminergic system has been implicated in diseases such as schizophrenia, Parkinson's disease, depression, attention deficit hyperactivity disorder, nausea and vomiting, among others. Dopamine's actions are mediated by a family of five G-protein coupled receptors (GPCRs) (viz. D1, D2, D3, D4 and D5)(1). The D2 dopamine receptor (DRD2) is the primary target for both typical(2) and atypical(3,4) antipsychotic drugs, and for Parkinson's disease drugs. Unfortunately, many drugs targeting DRD2 frequently cause serious and potentially life-threatening side effects due to promiscuous activities against related receptors(4,5). Accordingly, a molecular understanding of DRD2 structure and function could provide a template for the design of safer and more effective medications. Here we provide the crystal structure of DRD2 in complex with the widely prescribed atypical antipsychotic drug risperidone. The DRD2-risperidone structure reveals an unexpected mode of antipsychotic drug binding to dopamine receptors, and illuminates structural determinants essential for the actions of risperidone and related drugs at DRD2.
Structure of the D2 dopamine receptor bound to the atypical antipsychotic drug risperidone.,Wang S, Che T, Levit A, Shoichet BK, Wacker D, Roth BL Nature. 2018 Jan 24. pii: nature25758. doi: 10.1038/nature25758. PMID:29466326[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Albizu L, Holloway T, Gonzalez-Maeso J, Sealfon SC. Functional crosstalk and heteromerization of serotonin 5-HT2A and dopamine D2 receptors. Neuropharmacology. 2011 Sep;61(4):770-7. doi: 10.1016/j.neuropharm.2011.05.023., Epub 2011 May 27. PMID:21645528 doi:http://dx.doi.org/10.1016/j.neuropharm.2011.05.023
- ↑ Johnston CA, Siderovski DP. Structural basis for nucleotide exchange on G alpha i subunits and receptor coupling specificity. Proc Natl Acad Sci U S A. 2007 Feb 6;104(6):2001-6. Epub 2007 Jan 30. PMID:17264214
- ↑ Wang S, Che T, Levit A, Shoichet BK, Wacker D, Roth BL. Structure of the D2 dopamine receptor bound to the atypical antipsychotic drug risperidone. Nature. 2018 Jan 24. pii: nature25758. doi: 10.1038/nature25758. PMID:29466326 doi:http://dx.doi.org/10.1038/nature25758
