PDBsum entry 5osc

Transport protein

PDB id: 5osc

Contents

Protein chains

312 a.a.

Ligands

ACT ×8

A8W ×5

Y01 ×5

Metals

_CL ×5

PDB id:

5osc

Name:

Transport protein

Title:

Glic-gabaar alpha1 chimera crystallized in complex with pregnenolone sulfate at ph 4.5

Structure:

Proton-gated ion channel,gamma-aminobutyric acid receptor subunit alpha-2,gamma-aminobutyric acid receptor subunit alpha-1. Chain: a, b, c, d, e. Synonym: glic,ligand-gated ion channel,lgic,gaba(a) receptor subunit alpha-2,gaba(a) receptor subunit alpha-1. Engineered: yes

Source:

Gloeobacter violaceus (strain pcc 7421), mus musculus. Mouse. Organism_taxid: 251221, 10090. Strain: pcc 7421. Gene: glvi, glr4197, gabra2, gabra-2, gabra1, gabra-1. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108

Resolution:

3.10Å R-factor: 0.213 R-free: 0.246

Authors:

D.C.Laverty,M.G.Gold,T.G.Smart

Key ref:

D.Laverty et al. (2017). Crystal structures of a GABA_A-receptor chimera reveal new endogenous neurosteroid-binding sites. Nat Struct Mol Biol, 24, 977-985. PubMed id: 28967882

Date:

17-Aug-17 Release date: 11-Oct-17

Protein chains

P62812  (GBRA1_MOUSE) -  Gamma-aminobutyric acid receptor subunit alpha-1 from Mus musculus

Seq: 455 a.a.

Struc: 312 a.a.*

Protein chains

Q7NDN8  (GLIC_GLOVI) -  Proton-gated ion channel from Gloeobacter violaceus (strain ATCC 29082 / PCC 7421)

Seq: 359 a.a.

Struc: 312 a.a.*

* PDB and UniProt seqs differ at 234 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.?

Nat Struct Mol Biol 24:977-985 (2017)

PubMed id: 28967882

Crystal structures of a GABA_A-receptor chimera reveal new endogenous neurosteroid-binding sites.

D.Laverty, P.Thomas, M.Field, O.J.Andersen, M.G.Gold, P.C.Biggin, M.Gielen, T.G.Smart.

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.