Measurement of Conformational Changes accompanying Desensitization in an Ionotropic Glutamate Receptor

Neali Armstrong, Jaysankar Jasti, Mads Beich-Frandsen, Eric Gouaux

Research output: Contribution to journalArticle

161 Citations (Scopus)

Abstract

The canonical conformational states occupied by most ligand-gated ion channels, and many cell-surface receptors, are the resting, activated, and desensitized states. While the resting and activated states of multiple receptors are well characterized, elaboration of the structural properties of the desensitized state, a state that is by definition inactive, has proven difficult. Here we use electrical, chemical, and crystallographic experiments on the AMPA-sensitive GluR2 receptor, defining the conformational rearrangements of the agonist binding cores that occur upon desensitization of this ligand-gated ion channel. These studies demonstrate that desensitization involves the rupture of an extensive interface between domain 1 of 2-fold related glutamate-binding core subunits, compensating for the ca. 21° of domain closure induced by glutamate binding. The rupture of the domain 1 interface allows the ion channel to close and thereby provides a simple explanation to the long-standing question of how agonist binding is decoupled from ion channel gating upon receptor desensitization.

Original languageEnglish (US)
Pages (from-to)85-97
Number of pages13
JournalCell
Volume127
Issue number1
DOIs
StatePublished - Oct 6 2006
Externally publishedYes

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Ligand-Gated Ion Channels
Ionotropic Glutamate Receptors
Ion Channels
Rupture
Glutamic Acid
Ion Channel Gating
alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
Cell Surface Receptors
Structural properties
Experiments
AMPA 2 glutamate receptor ionotropic

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Measurement of Conformational Changes accompanying Desensitization in an Ionotropic Glutamate Receptor. / Armstrong, Neali; Jasti, Jaysankar; Beich-Frandsen, Mads; Gouaux, Eric.

In: Cell, Vol. 127, No. 1, 06.10.2006, p. 85-97.

Research output: Contribution to journalArticle

Armstrong, Neali ; Jasti, Jaysankar ; Beich-Frandsen, Mads ; Gouaux, Eric. / Measurement of Conformational Changes accompanying Desensitization in an Ionotropic Glutamate Receptor. In: Cell. 2006 ; Vol. 127, No. 1. pp. 85-97.
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