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

Neali Armstrong, Eric Gouaux

Research output: Contribution to journalArticle

736 Citations (Scopus)

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 ≃ 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°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.

Original languageEnglish (US)
Pages (from-to)165-181
Number of pages17
JournalNeuron
Volume28
Issue number1
StatePublished - 2000
Externally publishedYes

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alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
Glutamate Receptors
Ligands
Kainic Acid
Glutamic Acid
Excitatory Amino Acid Agonists
Contracts
Binding Sites
Peptides

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Mechanisms for activation and antagonism of an AMPA-sensitive glutamate receptor : Crystal structures of the GluR2 ligand binding core. / Armstrong, Neali; Gouaux, Eric.

In: Neuron, Vol. 28, No. 1, 2000, p. 165-181.

Research output: Contribution to journalArticle

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