Structural Mechanisms of Gating in Ionotropic Glutamate Receptors

Edward C. Twomey, Alexander I. Sobolevsky

Research output: Contribution to journalReview articlepeer-review

Abstract

Ionotropic glutamate receptors (iGluRs) are ligand-gated ion channels that mediate the majority of excitatory neurotransmission in the central nervous system. iGluRs open their ion channels in response to binding of the neurotransmitter glutamate, rapidly depolarize the postsynaptic neuronal membrane, and initiate signal transduction. Recent studies using X-ray crystallography and cryo-electron microscopy have determined full-length iGluR structures that (1) uncover the receptor architecture in an unliganded, resting state, (2) reveal conformational changes produced by ligands in order to activate iGluRs, open their ion channels, and conduct ions, and (3) show how activated, glutamate-bound iGluRs can adopt a nonconducting desensitized state. These new findings, combined with the results of previous structural and functional experiments, kinetic and molecular modeling, mutagenesis, and biochemical analyses, provide new views on the structural mechanisms of iGluR gating.

Original languageEnglish (US)
Pages (from-to)267-276
Number of pages10
JournalBiochemistry
Volume57
Issue number3
DOIs
StatePublished - Jan 23 2018
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry

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