PDBsum entry 7cmu

Membrane protein

PDB id: 7cmu

Contents

Protein chains

225 a.a.

337 a.a.

58 a.a.

231 a.a.

272 a.a.

Ligands

G6L

PDB id:

7cmu

Name:

Membrane protein

Title:

Dopamine receptor d3r-gi-pramipexole complex

Structure:

Guanine nucleotide-binding protein g(i) subunit alpha-1. Chain: a. Synonym: adenylate cyclase-inhibiting g alpha protein. Engineered: yes. Mutation: yes. Guanine nucleotide-binding protein g(i)/g(s)/g(t) subunit beta-1. Chain: b. Synonym: transducin beta chain 1.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: gnai1. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Gene: gnb1. Gene: gng2. Mus musculus.

Authors:

P.Xu,S.Huang,C.Mao,B.Krumm,X.Zhou,Y.Tan,X.-P.Huang,Y.Liu,D.-D.Shen, Y.Jiang,X.Yu,H.Jiang,K.Melcher,B.Roth,X.Cheng,Y.Zhang,H.Xu

Key ref:

P.Xu et al. (2021). Structures of the human dopamine D3 receptor-G_i complexes. Mol Cell, 81, 1147. PubMed id: 33548201 DOI: 10.1016/j.molcel.2021.01.003

Date:

29-Jul-20 Release date: 10-Mar-21

Protein chain

P63096  (GNAI1_HUMAN) -  Guanine nucleotide-binding protein G(i) subunit alpha-1 from Homo sapiens

Seq: 354 a.a.

Struc: 225 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: 337 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: 58 a.a.

Protein chain

No UniProt id for this chain

Struc: 231 a.a.

Protein chain

P0ABE7  (C562_ECOLX) -  Soluble cytochrome b562 from Escherichia coli

Seq: 128 a.a.

Struc: 272 a.a.*

Protein chain

P35462  (DRD3_HUMAN) -  D(3) dopamine receptor from Homo sapiens

Seq: 400 a.a.

Struc: 272 a.a.

* PDB and UniProt seqs differ at 120 residue positions (black crosses)

Enzyme reactions

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

DOI no: 10.1016/j.molcel.2021.01.003

Mol Cell 81:1147 (2021)

PubMed id: 33548201

Structures of the human dopamine D3 receptor-G_i complexes.

P.Xu, S.Huang, C.Mao, B.E.Krumm, X.E.Zhou, Y.Tan, X.P.Huang, Y.Liu, D.D.Shen, Y.Jiang, X.Yu, H.Jiang, K.Melcher, B.L.Roth, X.Cheng, Y.Zhang, H.E.Xu.

ABSTRACT

The dopamine system, including five dopamine receptors (D1R-D5R), plays essential roles in the central nervous system (CNS), and ligands that activate dopamine receptors have been used to treat many neuropsychiatric disorders. Here, we report two cryo-EM structures of human D3R in complex with an inhibitory G protein and bound to the D3R-selective agonists PD128907 and pramipexole, the latter of which is used to treat patients with Parkinson's disease. The structures reveal agonist binding modes distinct from the antagonist-bound D3R structure and conformational signatures for ligand-induced receptor activation. Mutagenesis and homology modeling illuminate determinants of ligand specificity across dopamine receptors and the mechanisms for G_i protein coupling. Collectively our work reveals the basis of agonist binding and ligand-induced receptor activation and provides structural templates for designing specific ligands to treat CNS diseases targeting the dopaminergic system.