4F12

Crystal structure of the extracellular domain of human GABA(B) receptor GBR2

Summary for 4F12

• Entry DOI: 10.2210/pdb4f12/pdb
• Related: 4F11
• Descriptor: Gamma-aminobutyric acid type B receptor subunit 2, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total)
• Functional Keywords: venus flytrap module, g-protein coupled receptor, signaling protein
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 50361.66

Authors

Geng, Y.,Xiong, D.,Mosyak, L.,Malito, D.L.,Kniazeff, J.,Chen, Y.,Burmakina, S.,Quick, M.,Bush, M.,Javitch, J.A.,Pin, J.-P.,Fan, Q.R. (deposition date: 2012-05-05, release date: 2012-06-06, Last modification date: 2024-10-30)

Primary citation

Geng, Y.,Xiong, D.,Mosyak, L.,Malito, D.L.,Kniazeff, J.,Chen, Y.,Burmakina, S.,Quick, M.,Bush, M.,Javitch, J.A.,Pin, J.P.,Fan, Q.R.
Structure and functional interaction of the extracellular domain of human GABA(B) receptor GBR2.
Nat.Neurosci., 15:970-978, 2012

PubMed Abstract: Inhibitory neurotransmission is mediated primarily by GABA. The metabotropic GABA(B) receptor is a G protein-coupled receptor central to mammalian brain function. Malfunction of GABA(B) receptor has been implicated in several neurological disorders. GABA(B) receptor functions as a heterodimeric assembly of GBR1 and GBR2 subunits, where GBR1 is responsible for ligand-binding and GBR2 is responsible for G protein coupling. Here we demonstrate that the GBR2 ectodomain directly interacts with the GBR1 ectodomain to increase agonist affinity by selectively stabilizing the agonist-bound conformation of GBR1. We present the crystal structure of the GBR2 ectodomain, which reveals a polar heterodimeric interface. We also identify specific heterodimer contacts from both subunits, and GBR1 residues involved in ligand recognition. Lastly, our structural and functional data indicate that the GBR2 ectodomain adopts a constitutively open conformation, suggesting a structural asymmetry in the active state of GABA(B) receptor that is unique to the GABAergic system.

PubMed: 22660477
DOI: 10.1038/nn.3133

Experimental method

X-RAY DIFFRACTION (3.02 Å)