PDBsum entry 6vms

Signaling protein

PDB id: 6vms

Contents

Protein chains

227 a.a.

339 a.a.

59 a.a.

232 a.a.

278 a.a.

Ligands

08Y

PDB id:

6vms

Name:

Signaling protein

Title:

Structure of a d2 dopamine receptor-g-protein complex in a lipid membrane

Structure:

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

Source:

Rattus norvegicus. Rat. Organism_taxid: 10116. Gene: gnai1, gnai-1. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Homo sapiens. Human. Organism_taxid: 9606.

Authors:

J.Yin,K.M.Chen,M.J.Clark,M.Hijazi,P.Kumari,X.Bai,R.K.Sunahara, P.Barth,D.M.Rosenbaum

Key ref:

J.Yin et al. (2020). Structure of a D2 dopamine receptor-G-protein complex in a lipid membrane. Nature, 584, 125-129. PubMed id: 32528175 DOI: 10.1038/s41586-020-2379-5

Date:

28-Jan-20 Release date: 17-Jun-20

Protein chain

P10824  (GNAI1_RAT) -  Guanine nucleotide-binding protein G(i) subunit alpha-1 from Rattus norvegicus

Seq: 354 a.a.

Struc: 227 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: 59 a.a.

Protein chain

No UniProt id for this chain

Struc: 232 a.a.

Protein chain

D9IEF7  (D9IEF7_BPT4) -  Endolysin from Enterobacteria phage T4

Seq: 164 a.a.

Struc: 278 a.a.*

Protein chain

P14416  (DRD2_HUMAN) -  D(2) dopamine receptor from Homo sapiens

Seq: 443 a.a.

Struc: 278 a.a.*

* PDB and UniProt seqs differ at 157 residue positions (black crosses)

Enzyme reactions

• Enzyme class 1: Chain A: E.C.3.6.5.- - ?????
• Enzyme class 2: Chain R: E.C.3.2.1.17 - lysozyme.
• Reaction: Hydrolysis of the 1,4-beta-linkages between N-acetyl-D-glucosamine and N-acetylmuramic acid in peptidoglycan heteropolymers of the prokaryotes cell walls.

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

DOI no: 10.1038/s41586-020-2379-5

Nature 584:125-129 (2020)

PubMed id: 32528175

Structure of a D2 dopamine receptor-G-protein complex in a lipid membrane.

J.Yin, K.M.Chen, M.J.Clark, M.Hijazi, P.Kumari, X.C.Bai, R.K.Sunahara, P.Barth, D.M.Rosenbaum.

ABSTRACT

The D2 dopamine receptor (DRD2) is a therapeutic target for Parkinson's disease¹ and antipsychotic drugs². DRD2 is activated by the endogenous neurotransmitter dopamine and synthetic agonist drugs such as bromocriptine³, leading to stimulation of G_i and inhibition of adenylyl cyclase. Here we used cryo-electron microscopy to elucidate the structure of an agonist-bound activated DRD2-G_i complex reconstituted into a phospholipid membrane. The extracellular ligand-binding site of DRD2 is remodelled in response to agonist binding, with conformational changes in extracellular loop 2, transmembrane domain 5 (TM5), TM6 and TM7, propagating to opening of the intracellular G_i-binding site. The DRD2-G_i structure represents, to our knowledge, the first experimental model of a G-protein-coupled receptor-G-protein complex embedded in a phospholipid bilayer, which serves as a benchmark to validate the interactions seen in previous detergent-bound structures. The structure also reveals interactions that are unique to the membrane-embedded complex, including helix 8 burial in the inner leaflet, ordered lysine and arginine side chains in the membrane interfacial regions, and lipid anchoring of the G protein in the membrane. Our model of the activated DRD2 will help to inform the design of subtype-selective DRD2 ligands for multiple human central nervous system disorders.