4MS3

Crystal structure of the extracellular domain of human GABA(B) receptor bound to the endogenous agonist GABA

Summary for 4MS3

• Entry DOI: 10.2210/pdb4ms3/pdb
• Related: 4MQE 4MQF 4MR7 4MR8 4MR9 4MRM 4MS1 4MS4
• Descriptor: Gamma-aminobutyric acid type B receptor subunit 1, Gamma-aminobutyric acid type B receptor subunit 2, GAMMA-AMINO-BUTANOIC ACID, ... (5 entities in total)
• Functional Keywords: heterodimeric protein complex, venus flytrap module, neurotransmitter receptor, signaling protein-agonist complex, signaling protein/agonist
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 2
• Total formula weight: 97097.47

Authors

Geng, Y.,Bush, M.,Mosyak, L.,Wang, F.,Fan, Q.R. (deposition date: 2013-09-18, release date: 2013-12-11, Last modification date: 2024-11-27)

Primary citation

Geng, Y.,Bush, M.,Mosyak, L.,Wang, F.,Fan, Q.R.
Structural mechanism of ligand activation in human GABA(B) receptor.
Nature, 504:254-259, 2013

PubMed 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.

PubMed: 24305054
DOI: 10.1038/nature12725

Experimental method

X-RAY DIFFRACTION (2.5 Å)