PDBsum entry 5ojm

Membrane protein

PDB id: 5ojm

Contents

Protein chains

330 a.a.

123 a.a.

Ligands

NAG-NAG-BMA-MAN-MAN ×3

NAG-NAG-BMA-MAN-MAN-MAN ×2

NAG ×5

PDB id:

5ojm

Name:

Membrane protein

Title:

Structure of a chimaeric beta3-alpha5 gabaa receptor in complex with nanobody nb25

Structure:

Human gabaa receptor chimera beta3-alpha5,gamma- aminobutyric acid receptor subunit beta-3,gamma-aminobutyric acid receptor subunit alpha-5. Chain: a, b, c, d, e. Synonym: gaba(a) receptor subunit beta-3,gaba(a) receptor subunit alpha-5. Engineered: yes. Other_details: this is a chimaeric construct, containing the secretion signal sequence from phlsec vector (pmid: 17001101), the

Source:

Synthetic construct, homo sapiens. Human. Organism_taxid: 32630, 9606. Gene: gabrb3, gabra5. Expressed in: homo sapiens. Expression_system_taxid: 9606. Expression_system_cell_line: hek-293s gnti-. Expression_system_atcc_number: crl-3022. Lama glama.

Resolution:

3.30Å R-factor: 0.234 R-free: 0.250

Authors:

P.S.Miller,S.Scott,S.Masiulis,L.De Colibus,E.Pardon,J.Steyaert, A.R.Aricescu

Key ref:

P.S.Miller et al. (2017). Structural basis for GABA_Areceptor potentiation by neurosteroids. Nat Struct Mol Biol, 24, 986-992. PubMed id: 28991263

Date:

21-Jul-17 Release date: 04-Oct-17

Protein chains

P28472  (GBRB3_HUMAN) -  Gamma-aminobutyric acid receptor subunit beta-3 from Homo sapiens

Seq: 473 a.a.

Struc: 330 a.a.*

Protein chains

P31644  (GBRA5_HUMAN) -  Gamma-aminobutyric acid receptor subunit alpha-5 from Homo sapiens

Seq: 462 a.a.

Struc: 330 a.a.*

Protein chains

No UniProt id for this chain

Struc: 123 a.a.

* PDB and UniProt seqs differ at 208 residue positions (black crosses)

Nat Struct Mol Biol 24:986-992 (2017)

PubMed id: 28991263

Structural basis for GABA_Areceptor potentiation by neurosteroids.

P.S.Miller, S.Scott, S.Masiulis, L.De Colibus, E.Pardon, J.Steyaert, A.R.Aricescu.

ABSTRACT

Type A γ-aminobutyric acid receptors (GABA_ARs) are the principal mediators of inhibitory neurotransmission in the human brain. Endogenous neurosteroids interact with GABA_ARs to regulate acute and chronic anxiety and are potent sedative, analgesic, anticonvulsant and anesthetic agents. Their mode of binding and mechanism of receptor potentiation, however, remain unknown. Here we report crystal structures of a chimeric GABA_AR construct in apo and pregnanolone-bound states. The neurosteroid-binding site is mechanically coupled to the helices lining the ion channel pore and modulates the desensitization-gate conformation. We demonstrate that the equivalent site is responsible for physiological, heteromeric GABA_AR potentiation and explain the contrasting modulatory properties of 3a versus 3b neurosteroid epimers. These results illustrate how peripheral lipid ligands can regulate the desensitization gate of GABA_ARs, a process of broad relevance to pentameric ligand-gated ion channels.