PDBsum entry 4uqk

Transport protein

PDB id: 4uqk

Contents

Protein chains

631 a.a.

Ligands

QUS ×4

PDB id:

4uqk

Name:

Transport protein

Title:

Electron density map of glua2em in complex with quisqualate and ly451646

Structure:

Glutamate receptor 2. Chain: a, b, c, d. Fragment: residues 22-847. Synonym: glur-2, ampa-selective glutamate receptor 2, glur-b, glur-k 2, glutamate receptor ionotropic, ampa 2, glua2. Engineered: yes

Source:

Rattus norvegicus. Norway rat. Organism_taxid: 10116. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Expression_system_cell_line: sf9.

Authors:

J.R.Meyerson,J.Kumar,S.Chittori,P.Rao,J.Pierson,A.Bartesaghi, M.L.Mayer,S.Subramaniam

Key ref:

J.R.Meyerson et al. (2014). Structural mechanism of glutamate receptor activation and desensitization. Nature, 514, 328-334. PubMed id: 25119039 DOI: 10.1038/nature13603

Date:

24-Jun-14 Release date: 13-Aug-14

Protein chains

P19491  (GRIA2_RAT) -  Glutamate receptor 2 from Rattus norvegicus

Seq: 883 a.a.

Struc: 631 a.a.*

* PDB and UniProt seqs differ at 3 residue positions (black crosses)

DOI no: 10.1038/nature13603

Nature 514:328-334 (2014)

PubMed id: 25119039

Structural mechanism of glutamate receptor activation and desensitization.

J.R.Meyerson, J.Kumar, S.Chittori, P.Rao, J.Pierson, A.Bartesaghi, M.L.Mayer, S.Subramaniam.

ABSTRACT

Ionotropic glutamate receptors are ligand-gated ion channels that mediate excitatory synaptic transmission in the vertebrate brain. To gain a better understanding of how structural changes gate ion flux across the membrane, we trapped rat AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) and kainate receptor subtypes in their major functional states and analysed the resulting structures using cryo-electron microscopy. We show that transition to the active state involves a 'corkscrew' motion of the receptor assembly, driven by closure of the ligand-binding domain. Desensitization is accompanied by disruption of the amino-terminal domain tetramer in AMPA, but not kainate, receptors with a two-fold to four-fold symmetry transition in the ligand-binding domains in both subtypes. The 7.6 Å structure of a desensitized kainate receptor shows how these changes accommodate channel closing. These findings integrate previous physiological, biochemical and structural analyses of glutamate receptors and provide a molecular explanation for key steps in receptor gating.