PDBsum entry 1fto

Membrane protein

PDB id: 1fto

Contents

Protein chains

257 a.a. *

Waters ×245

* Residue conservation analysis

PDB id:

1fto

Name:

Membrane protein

Title:

Crystal structure of the glur2 ligand binding core (s1s2j) in the apo state at 2.0 a resolution

Structure:

Glutamate receptor subunit 2. Chain: a, b. Fragment: ligand binding core (s1s2j). Synonym: glur-2. Engineered: yes

Source:

Rattus norvegicus. Norway rat. Organism_taxid: 10116. Organ: brain. Expressed in: escherichia coli. Expression_system_taxid: 562.

Biol. unit:

Dimer (from PQS)

Resolution:

2.00Å R-factor: 0.224 R-free: 0.287

Authors:

N.Armstrong,E.Gouaux

Key ref:

N.Armstrong and E.Gouaux (2000). Mechanisms for activation and antagonism of an AMPA-sensitive glutamate receptor: crystal structures of the GluR2 ligand binding core. Neuron, 28, 165-181. PubMed id: 11086992 DOI: 10.1016/S0896-6273(00)00094-5

Date:

12-Sep-00 Release date: 01-Nov-00

Protein chains

P19491  (GRIA2_RAT) -  Glutamate receptor 2 from Rattus norvegicus

Seq: 883 a.a.

Struc: 257 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

DOI no: 10.1016/S0896-6273(00)00094-5

Neuron 28:165-181 (2000)

PubMed id: 11086992

Mechanisms for activation and antagonism of an AMPA-sensitive glutamate receptor: crystal structures of the GluR2 ligand binding core.

N.Armstrong, E.Gouaux.

ABSTRACT

Crystal structures of the GluR2 ligand binding core (S1S2) have been determined in the apo state and in the presence of the antagonist DNQX, the partial agonist kainate, and the full agonists AMPA and glutamate. The domains of the S1S2 ligand binding core are expanded in the apo state and contract upon ligand binding with the extent of domain separation decreasing in the order of apo > DNQX > kainate > glutamate approximately equal to AMPA. These results suggest that agonist-induced domain closure gates the transmembrane channel and the extent of receptor activation depends upon the degree of domain closure. AMPA and glutamate also promote a 180 degrees flip of a trans peptide bond in the ligand binding site. The crystal packing of the ligand binding cores suggests modes for subunit-subunit contact in the intact receptor and mechanisms by which allosteric effectors modulate receptor activity.

Selected figure(s)

Figure 1.
Figure 1. Ligand Binding Constants for S1S2J(A) Domain structure of iGluRs showing the S1 and S2 segments in turquoise and pink, respectively. “Cut” and “link” denote the edges of the S1S2 construct.(B) K[D] for ^3H-AMPA binding was 24.8 ± 1.8 nM.(C) IC[50] for displacement of ^3H-AMPA by glutamate, kainate, and DNQX were 821 nM, 14.5 μM, and 998 nM, respectively.

Figure 2.
Figure 2. Superposition of the Expanded Cleft Structures and Stereo View of the DNQX Binding Site(A) The two apo molecules (ApoA and ApoB) and two DNQX molecules (DNQXA and DNQXB) in each asymmetric unit were superimposed using only Cα atoms from domain 1. Apo protomers are shaded red and pink while DNQX protomers are colored light green and dark green. DNQX is depicted in black, and selected side chains from DNQXB are shown in dark green. The conformational change undergone by Glu-705 is illustrated by comparing its orientation in ApoB and DNQXB. In the apo state, Glu-705 accepts hydrogen bonds from the side chains of Lys-730 and Thr-655.(B) The chemical structure of DNQX and F[o]-F[c] omit electron density for DNQX and sulfate contoured at 2.5 σ.(C) Stereo image of the interactions between DNQX, sulfate, and S1S2J. DNQXB side chains are colored gray. Water molecules are shown as green balls. DNQX is colored black. Hydrogen bonds between DNQX, sulfate, and S1S2J are indicated by black dashed lines.

The above figures are reprinted by permission from Cell Press: Neuron (2000, 28, 165-181) copyright 2000.

Figures were selected by an automated process.