PDBsum entry 4ms3

Signaling protein/agonist

PDB id: 4ms3

Contents

Protein chains

395 a.a.

408 a.a.

Ligands

ABU

NAG

Waters ×306

PDB id:

4ms3

Name:

Signaling protein/agonist

Title:

Crystal structure of the extracellular domain of human gaba(b) receptor bound to the endogenous agonist gaba

Structure:

Gamma-aminobutyric acid type b receptor subunit 1. Chain: a. Fragment: extracellular domain (see remark 999). Synonym: gaba-b receptor 1, gaba-b-r1, gaba-br1, gababr1, gb1. Engineered: yes. Gamma-aminobutyric acid type b receptor subunit 2. Chain: b. Fragment: extracellular domain (unp residues 42-466). Synonym: gaba-b receptor 2, gaba-b-r2, gaba-br2, gababr2, gb2, g-

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: gabbr1, gprc3a. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Gene: gabbr2, gpr51, gprc3b.

Resolution:

2.50Å R-factor: 0.210 R-free: 0.232

Authors:

Y.Geng,M.Bush,L.Mosyak,F.Wang,Q.R.Fan

Key ref:

Y.Geng et al. (2013). Structural mechanism of ligand activation in human GABA(B) receptor. Nature, 504, 254-259. PubMed id: 24305054 DOI: 10.1038/nature12725

Date:

18-Sep-13 Release date: 11-Dec-13

Protein chain

Q9UBS5  (GABR1_HUMAN) -  Gamma-aminobutyric acid type B receptor subunit 1 from Homo sapiens

Seq: 961 a.a.

Struc: 395 a.a.*

Protein chain

O75899  (GABR2_HUMAN) -  Gamma-aminobutyric acid type B receptor subunit 2 from Homo sapiens

Seq: 941 a.a.

Struc: 408 a.a.*

* PDB and UniProt seqs differ at 7 residue positions (black crosses)

DOI no: 10.1038/nature12725

Nature 504:254-259 (2013)

PubMed id: 24305054

Structural mechanism of ligand activation in human GABA(B) receptor.

Y.Geng, M.Bush, L.Mosyak, F.Wang, Q.R.Fan.

ABSTRACT

Human GABA(B) (γ-aminobutyric acid class B) receptor is a G-protein-coupled receptor central to inhibitory neurotransmission in the brain. It functions as an obligatory heterodimer of the subunits GBR1 and GBR2. Here we present the crystal structures of a heterodimeric complex between the extracellular domains of GBR1 and GBR2 in the apo, agonist-bound and antagonist-bound forms. The apo and antagonist-bound structures represent the resting state of the receptor; the agonist-bound complex corresponds to the active state. Both subunits adopt an open conformation at rest, and only GBR1 closes on agonist-induced receptor activation. The agonists and antagonists are anchored in the interdomain crevice of GBR1 by an overlapping set of residues. An antagonist confines GBR1 to the open conformation of the inactive state, whereas an agonist induces its domain closure for activation. Our data reveal a unique activation mechanism for GABA(B) receptor that involves the formation of a novel heterodimer interface between subunits.