4COF

Crystal structure of a human gamma-aminobutyric acid receptor, the GABA(A)R-beta3 homopentamer

Summary for 4COF

• Entry DOI: 10.2210/pdb4cof/pdb
• Descriptor: GAMMA-AMINOBUTYRIC ACID RECEPTOR SUBUNIT BETA-3, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, BENZAMIDINE, ... (5 entities in total)
• Functional Keywords: transport protein, membrane protein
• Biological source: HOMO SAPIENS (HUMAN)
• Total number of polymer chains: 5
• Total formula weight: 209197.77

Authors

Miller, P.S.,Aricescu, A.R. (deposition date: 2014-01-28, release date: 2014-06-04, Last modification date: 2024-11-06)

Primary citation

Miller, P.S.,Aricescu, A.R.
Crystal Structure of a Human Gabaa Receptor
Nature, 512:270-, 2014

PubMed Abstract: Type-A γ-aminobutyric acid receptors (GABAARs) are the principal mediators of rapid inhibitory synaptic transmission in the human brain. A decline in GABAAR signalling triggers hyperactive neurological disorders such as insomnia, anxiety and epilepsy. Here we present the first three-dimensional structure of a GABAAR, the human β3 homopentamer, at 3 Å resolution. This structure reveals architectural elements unique to eukaryotic Cys-loop receptors, explains the mechanistic consequences of multiple human disease mutations and shows an unexpected structural role for a conserved N-linked glycan. The receptor was crystallized bound to a previously unknown agonist, benzamidine, opening a new avenue for the rational design of GABAAR modulators. The channel region forms a closed gate at the base of the pore, representative of a desensitized state. These results offer new insights into the signalling mechanisms of pentameric ligand-gated ion channels and enhance current understanding of GABAergic neurotransmission.

PubMed: 24909990
DOI: 10.1038/NATURE13293

Experimental method

X-RAY DIFFRACTION (2.97 Å)