3b6t

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spinqualitylabelsall models 3b6t, resolution 2.10Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

Crystal Structure of the GLUR2 Ligand Binding Core (S1S2J) T686A Mutant in Complex with Quisqualate at 2.1 Resolution

Overview

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.

About this Structure

3B6T is a Single protein structure of sequence from Rattus norvegicus with and as ligands. Known structural/functional Sites: and . Full crystallographic information is available from OCA.

Reference

Structural and single-channel results indicate that the rates of ligand binding domain closing and opening directly impact AMPA receptor gating., Zhang W, Cho Y, Lolis E, Howe JR, J Neurosci. 2008 Jan 23;28(4):932-43. PMID:18216201

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