5OSC

GLIC-GABAAR alpha1 chimera crystallized in complex with pregnenolone sulfate at pH 4.5

Summary for 5OSC

• Entry DOI: 10.2210/pdb5osc/pdb
• Descriptor: Proton-gated ion channel,Gamma-aminobutyric acid receptor subunit alpha-2,Gamma-aminobutyric acid receptor subunit alpha-1, ACETATE ION, CHLORIDE ION, ... (5 entities in total)
• Functional Keywords: gabaa-receptor ion channel ion transport extracellular ligand gated ion channel, transport protein
• Biological source: Gloeobacter violaceus (strain PCC 7421); More
• Cellular location: Cell junction, synapse, postsynaptic cell membrane; Multi-pass membrane protein: P62812
• Total number of polymer chains: 5
• Total formula weight: 198286.85

Authors

Laverty, D.C.,Gold, M.G.,Smart, T.G. (deposition date: 2017-08-17, release date: 2017-10-11, Last modification date: 2024-01-17)

Primary citation

Laverty, D.,Thomas, P.,Field, M.,Andersen, O.J.,Gold, M.G.,Biggin, P.C.,Gielen, M.,Smart, T.G.
Crystal structures of a GABAA-receptor chimera reveal new endogenous neurosteroid-binding sites.
Nat. Struct. Mol. Biol., 24:977-985, 2017

PubMed Abstract: γ-Aminobutyric acid receptors (GABARs) are vital for controlling excitability in the brain. This is emphasized by the numerous neuropsychiatric disorders that result from receptor dysfunction. A critical component of most native GABARs is the α subunit. Its transmembrane domain is the target for many modulators, including endogenous brain neurosteroids that impact anxiety, stress and depression, and for therapeutic drugs, such as general anesthetics. Understanding the basis for the modulation of GABAR function requires high-resolution structures. Here we present the first atomic structures of a GABAR chimera at 2.8-Å resolution, including those bound with potentiating and inhibitory neurosteroids. These structures define new allosteric binding sites for these modulators that are associated with the α-subunit transmembrane domain. Our findings will enable the exploitation of neurosteroids for therapeutic drug design to regulate GABARs in neurological disorders.

PubMed: 28967882
DOI: 10.1038/nsmb.3477

Experimental method

X-RAY DIFFRACTION (3.1 Å)