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

162 Scopus citations

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

    Fingerprint

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this