PDBsum entry 4u5c

Transport protein/toxin

PDB id: 4u5c

Contents

Protein chains

747 a.a.

85 a.a.

Ligands

NAG ×4

FWD ×4

FWF ×2

PDB id:

4u5c

Name:

Transport protein/toxin

Title:

Crystal structure of glua2, con-ikot-ikot snail toxin, partial agonist fw and postitive modulator (r,r)-2b complex

Structure:

Glutamate receptor 2. Chain: a, b, c, d. Synonym: glur-2,ampa-selective glutamate receptor 2,glur-b,glur-k2, glutamate receptor ionotropic,ampa 2,glua2. Engineered: yes. Con-ikot-ikot. Chain: e, f. Engineered: yes

Source:

Rattus norvegicus. Rat. Organism_taxid: 10116. Gene: gria2, glur2. Expressed in: homo sapiens. Expression_system_taxid: 9606. Expression_system_cell_line: hek293s gnti-. Conus striatus. Striated cone.

Resolution:

3.69Å R-factor: 0.210 R-free: 0.254

Authors:

L.Chen,E.Gouaux

Key ref:

L.Chen et al. (2014). X-ray structures of AMPA receptor-cone snail toxin complexes illuminate activation mechanism. Science, 345, 1021-1026. PubMed id: 25103405 DOI: 10.1126/science.1258409

Date:

25-Jul-14 Release date: 13-Aug-14

Protein chains

P19491  (GRIA2_RAT) -  Glutamate receptor 2 from Rattus norvegicus

Seq: 883 a.a.

Struc: 747 a.a.*

Protein chains

P0CB20  (CONII_CONST) -  Con-ikot-ikot from Conus striatus

Seq: 123 a.a.

Struc: 85 a.a.

* PDB and UniProt seqs differ at 14 residue positions (black crosses)

DOI no: 10.1126/science.1258409

Science 345:1021-1026 (2014)

PubMed id: 25103405

X-ray structures of AMPA receptor-cone snail toxin complexes illuminate activation mechanism.

L.Chen, K.L.Dürr, E.Gouaux.

ABSTRACT

AMPA-sensitive glutamate receptors are crucial to the structural and dynamic properties of the brain, to the development and function of the central nervous system, and to the treatment of neurological conditions from depression to cognitive impairment. However, the molecular principles underlying AMPA receptor activation have remained elusive. We determined multiple x-ray crystal structures of the GluA2 AMPA receptor in complex with a Conus striatus cone snail toxin, a positive allosteric modulator, and orthosteric agonists, at 3.8 to 4.1 angstrom resolution. We show how the toxin acts like a straightjacket on the ligand-binding domain (LBD) "gating ring," restraining the domains via both intra- and interdimer cross-links such that agonist-induced closure of the LBD "clamshells" is transduced into an irislike expansion of the gating ring. By structural analysis of activation-enhancing mutants, we show how the expansion of the LBD gating ring results in pulling forces on the M3 helices that, in turn, are coupled to ion channel gating.