3B6W

Crystal Structure of the GLUR2 Ligand Binding Core (S1S2J) T686S Mutant in Complex with Glutamate at 1.7 Resolution

Summary for 3B6W

• Entry DOI: 10.2210/pdb3b6w/pdb
• Related: 1FTJ 1FTO 1P1U 3B6Q 3B6T
• Descriptor: Glutamate receptor 2, SULFATE ION, GLUTAMIC ACID, ... (4 entities in total)
• Functional Keywords: glur2, t686s, mutant, ampa receptor, ionotropic glutamate receptor, alternative splicing, cell junction, glycoprotein, ion transport, ionic channel, lipoprotein, membrane, palmitate, phosphorylation, postsynaptic cell membrane, rna editing, synapse, transmembrane, transport, membrane protein
• Biological source: Rattus norvegicus (Norway rat); More
• Cellular location: Cell membrane; Multi-pass membrane protein: P19491
• Total number of polymer chains: 4
• Total formula weight: 117509.14

Authors

Cho, Y.,Lolis, E.,Howe, J.R. (deposition date: 2007-10-29, release date: 2008-02-05, Last modification date: 2024-10-30)

Primary citation

Zhang, W.,Cho, Y.,Lolis, E.,Howe, J.R.
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, 2008

PubMed 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.

PubMed: 18216201
DOI: 10.1523/JNEUROSCI.3309-07.2008

Experimental method

X-RAY DIFFRACTION (1.7 Å)