PDBsum entry 3s9e

Membrane protein

PDB id: 3s9e

Contents

Protein chains

253 a.a.

Ligands

GLU ×2

GOL

PO4 ×3

Metals

_NA ×3

_CL ×4

Waters ×581

PDB id:

3s9e

Name:

Membrane protein

Title:

Crystal structure of the kainate receptor gluk3 ligand binding domain in complex with (s)-glutamate

Structure:

Glutamate receptor, ionotropic kainate 3. Chain: a, b. Engineered: yes

Source:

Rattus norvegicus. Rat. Organism_taxid: 10116. Gene: grik3. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

1.60Å R-factor: 0.138 R-free: 0.184

Authors:

R.Venskutonyte,K.Frydenvang,M.Gajhede,J.S.Kastrup

Key ref:

R.Venskutonytė et al. (2011). Binding site and interlobe interactions of the ionotropic glutamate receptor GluK3 ligand binding domain revealed by high resolution crystal structure in complex with (S)-glutamate. J Struct Biol, 176, 307-314. PubMed id: 21907808

Date:

01-Jun-11 Release date: 28-Sep-11

Protein chains

P42264  (GRIK3_RAT) -  Glutamate receptor ionotropic, kainate 3 from Rattus norvegicus

Seq: 919 a.a.

Struc: 253 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

J Struct Biol 176:307-314 (2011)

PubMed id: 21907808

Binding site and interlobe interactions of the ionotropic glutamate receptor GluK3 ligand binding domain revealed by high resolution crystal structure in complex with (S)-glutamate.

R.Venskutonytė, K.Frydenvang, M.Gajhede, L.Bunch, D.S.Pickering, J.S.Kastrup.

ABSTRACT

Ionotropic glutamate receptors (iGluRs) are involved in excitatory signal transmission throughout the central nervous system and their malfunction is associated with various health disorders. GluK3 is a subunit of iGluRs, belonging to the subfamily of kainate receptors (GluK1-5). Several crystal structures of GluK1 and GluK2 ligand binding domains have been determined in complex with agonists and antagonists. However, little is known about the molecular mechanisms underlying GluK3 ligand binding properties and no compounds displaying reasonable selectivity towards GluK3 are available today. Here, we present the first X-ray crystal structure of the ligand binding domain of GluK3 in complex with glutamate, determined to 1.6Å resolution. The structure reveals a conserved glutamate binding mode, characteristic for iGluRs, and a water molecule network in the glutamate binding site similar to that seen in GluK1. In GluK3, a slightly lower degree of domain closure around glutamate is observed compared to most other kainate receptor structures with glutamate. The volume of the GluK3 glutamate binding cavity was found to be of intermediate size between those of GluK1 and GluK2. The residues in GluK3 contributing to the subfamily differences in the binding sites are primarily: Thr520, Ala691, Asn722, Leu736 and Thr742. The GluK3 ligand binding domain seems to be less stabilized through interlobe interactions than GluK1 and this may contribute to the faster desensitization kinetics of GluK3.