7jvr

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Cryo-EM structure of Bromocriptine-bound dopamine receptor 2 in complex with Gi protein

Structural highlights

7jvr is a 5 chain structure with sequence from Escherichia coli, 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 2.8Å
Ligands:08Y
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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

C562_ECOLX Electron-transport protein of unknown function.DRD2_HUMAN Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase (By similarity).[1] [2]

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[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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Citations
15 reviews cite this structure
The neural basis of psychedelic action.
Kwan et al. (2022)
14 more
56 other articles
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See Also

References

  1. ↑ 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
  2. ↑ 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
  3. ↑ 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. Structural insights into the human D1 and D2 dopamine receptor signaling complexes. Cell. 2021 Feb 18;184(4):931-942.e18. PMID:33571431 doi:10.1016/j.cell.2021.01.027

Contents


PDB ID 7jvr

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OCA

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