PDBsum entry 7jv5

Signaling protein

PDB id: 7jv5

Contents

Protein chains

282 a.a.

238 a.a.

339 a.a.

57 a.a.

128 a.a.

Ligands

SK0

CLR ×6

PLM ×6

PDB id:

7jv5

Name:

Signaling protein

Title:

Cryo-em structure of skf-81297-bound dopamine receptor 1 in complex with gs protein

Structure:

D(1a) dopamine receptor. Chain: r. Synonym: dopamine d1 receptor. Engineered: yes. Guanine nucleotide-binding protein g(s) subunit alpha isoforms short. Chain: a. Synonym: adenylate cyclase-stimulating g alpha protein. Engineered: yes.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: drd1. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Gene: gnas, gnas1, gsp. Gene: gnb1. Gene: gng2.

Authors:

Y.Zhuang,P.Xu,C.Mao,L.Wang,B.Krumm,X.E.Zhou,S.Huang,H.Liu,X.Cheng,X.- P.Huang,D.-D.Sheng,T.Xu,Y.-F.Liu,Y.Wang,J.Guo,Y.Jiang,H.Jiang, K.Melcher,B.L.Roth,Y.Zhang,C.Zhang,H.E.Xu

Key ref:

Y.Zhuang et al. (2021). Structural insights into the human D1 and D2 dopamine receptor signaling complexes. Cell, 184, 931. PubMed id: 33571431 DOI: 10.1016/j.cell.2021.01.027

Date:

20-Aug-20 Release date: 24-Feb-21

Protein chain

P21728  (DRD1_HUMAN) -  D(1A) dopamine receptor from Homo sapiens

Seq: 446 a.a.

Struc: 282 a.a.

Protein chain

P63092  (GNAS2_HUMAN) -  Guanine nucleotide-binding protein G(s) subunit alpha isoforms short from Homo sapiens

Seq: 394 a.a.

Struc: 238 a.a.*

Protein chain

P62873  (GBB1_HUMAN) -  Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 from Homo sapiens

Seq: 340 a.a.

Struc: 339 a.a.

Protein chain

P59768  (GBG2_HUMAN) -  Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 from Homo sapiens

Seq: 71 a.a.

Struc: 57 a.a.

Protein chain

No UniProt id for this chain

Struc: 128 a.a.

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

Enzyme reactions

• Enzyme class: Chain A: E.C.3.6.5.- - ?????

DOI no: 10.1016/j.cell.2021.01.027

Cell 184:931 (2021)

PubMed id: 33571431

Structural insights into the human D1 and D2 dopamine receptor signaling complexes.

Y.Zhuang, P.Xu, C.Mao, L.Wang, B.Krumm, X.E.Zhou, S.Huang, H.Liu, X.Cheng, X.P.Huang, D.D.Shen, T.Xu, Y.F.Liu, Y.Wang, J.Guo, Y.Jiang, H.Jiang, K.Melcher, B.L.Roth, Y.Zhang, C.Zhang, H.E.Xu.

ABSTRACT

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.