PDBsum entry 5osc

Transport protein

PDB id: 5osc

Contents

Protein chains

312 a.a.

Ligands

ACT ×8

A8W ×5

Y01 ×5

Metals

_CL ×5

References listed in PDB file

Key reference

• Title: Crystal structures of a gaba_a-Receptor chimera reveal new endogenous neurosteroid-Binding sites.
• Authors: D.Laverty, P.Thomas, M.Field, O.J.Andersen, M.G.Gold, P.C.Biggin, M.Gielen, T.G.Smart.
• Ref.: Nat Struct Mol Biol, 2017, 24, 977-985.
• PubMed id: 28967882

Abstract

γ-Aminobutyric acid receptors (GABA_ARs) 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 GABA_ARs 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 GABA_AR function requires high-resolution structures. Here we present the first atomic structures of a GABA_AR 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 GABA_ARs in neurological disorders.