2GFE

Crystal structure of the GluR2 A476E S673D Ligand Binding Core Mutant at 1.54 Angstroms Resolution

Summary for 2GFE

• Entry DOI: 10.2210/pdb2gfe/pdb
• Related: 1FTJ 1S50 2F36
• Descriptor: Glutamate receptor 2, ZINC ION, GLUTAMIC ACID, ... (4 entities in total)
• Functional Keywords: membrane protein
• Biological source: Rattus norvegicus (Norway rat); More
• Cellular location: Cell membrane; Multi-pass membrane protein: P19491
• Total number of polymer chains: 3
• Total formula weight: 88430.39

Authors

Mayer, M.L. (deposition date: 2006-03-21, release date: 2006-08-22, Last modification date: 2023-08-30)

Primary citation

Weston, M.C.,Gertler, C.,Mayer, M.L.,Rosenmund, C.
Interdomain interactions in AMPA and kainate receptors regulate affinity for glutamate.
J.Neurosci., 26:7650-7658, 2006

PubMed Abstract: Ionotropic glutamate receptors perform diverse functions in the nervous system. As a result, multiple receptor subtypes have evolved with different kinetics, ion permeability, expression patterns, and regulation by second messengers. Kainate receptors show slower recovery from desensitization and have different affinities for agonists than AMPA receptors. Based on analysis of ligand binding domain crystal structures, we identified interdomain interactions in the agonist-bound state that are conserved in kainate receptors and absent in AMPA receptors. Mutations in GluR6 designed to disrupt these contacts reduced agonist apparent affinity, speeded up receptor deactivation and increased the rate of recovery from desensitization. Conversely, introduction of mutations in GluR2 that enabled additional interdomain interactions in the agonist-bound state increased agonist apparent affinity 15-fold, and slowed both deactivation and recovery from desensitization. We conclude that interdomain interactions have evolved as a distinct mechanism that contributes to the unique kinetic properties of AMPA and kainate receptors.

PubMed: 16855092
DOI: 10.1523/JNEUROSCI.1519-06.2006

Experimental method

X-RAY DIFFRACTION (1.54 Å)