PDBsum entry 3b6t

Membrane protein

PDB id: 3b6t

Contents

Protein chain

258 a.a. *

Ligands

SO4

QUS

Waters ×157

* Residue conservation analysis

PDB id:

3b6t

Name:

Membrane protein

Title:

Crystal structure of the glur2 ligand binding core (s1s2j) t686a mutant in complex with quisqualate at 2.1 resolution

Structure:

Glutamate receptor 2. Chain: a. Synonym: glur-2, glur-b, glur-k2, glutamate receptor ionotropic, ampa 2, ampa-selective glutamate receptor 2. Engineered: yes. Mutation: yes

Source:

Rattus norvegicus. Norway rat. Organism_taxid: 10116. Gene: gria2, glur2. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

2.10Å R-factor: 0.209 R-free: 0.274

Authors:

Y.Cho,E.Lolis,J.R.Howe

Key ref:

W.Zhang et al. (2008). Structural and single-channel results indicate that the rates of ligand binding domain closing and opening directly impact AMPA receptor gating. J Neurosci, 28, 932-943. PubMed id: 18216201

Date:

29-Oct-07 Release date: 05-Feb-08

Protein chain

P19491  (GRIA2_RAT) -  Glutamate receptor 2 from Rattus norvegicus

Seq: 883 a.a.

Struc: 258 a.a.*

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

J Neurosci 28:932-943 (2008)

PubMed id: 18216201

Structural and single-channel results indicate that the rates of ligand binding domain closing and opening directly impact AMPA receptor gating.

W.Zhang, Y.Cho, E.Lolis, J.R.Howe.

ABSTRACT

At most excitatory central synapses, glutamate is released from presynaptic terminals and binds to postsynaptic AMPA receptors, initiating a series of conformational changes that result in ion channel opening. Efficient transmission at these synapses requires that glutamate binding to AMPA receptors results in rapid and near-synchronous opening of postsynaptic receptor channels. In addition, if the information encoded in the frequency of action potential discharge is to be transmitted faithfully, glutamate must dissociate from the receptor quickly, enabling the synapse to discriminate presynaptic action potentials that are spaced closely in time. The current view is that the efficacy of agonists is directly related to the extent to which ligand binding results in closure of the binding domain. For glutamate to dissociate from the receptor, however, the binding domain must open. Previously, we showed that mutations in glutamate receptor subunit 2 that should destabilize the closed conformation not only sped deactivation but also altered the relative efficacy of glutamate and quisqualate. Here we present x-ray crystallographic and single-channel data that support the conclusions that binding domain closing necessarily precedes channel opening and that the kinetics of conformational changes at the level of the binding domain importantly influence ion channel gating. Our findings suggest that the stability of the closed-cleft conformation has been tuned during evolution so that glutamate dissociates from the receptor as rapidly as possible but remains an efficacious agonist.