Emerging structural insights into the function of ionotropic glutamate receptors

Trends Biochem Sci. 2015 Jun;40(6):328-37. doi: 10.1016/j.tibs.2015.04.002. Epub 2015 May 1.

Abstract

Ionotropic glutamate receptors (iGluRs) are ligand-gated ion channels that mediate excitatory neurotransmission crucial for brain development and function, including learning and memory formation. Recently a wealth of structural studies on iGluRs including AMPA receptors (AMPARs), kainate receptors, and NMDA receptors (NMDARs) became available. These studies showed structures of non-NMDARs including AMPAR and kainate receptor in various functional states, thereby providing the first visual sense of how non-NMDAR iGluRs may function in the context of homotetramers. Furthermore, they provided the first view of heterotetrameric NMDAR ion channels, and this illuminated the similarities with and differences from non-NMDARs, thus raising a mechanistic distinction between the two groups of iGluRs. We review mechanistic insights into iGluR functions gained through structural studies of multiple groups.

Keywords: ionotropic glutamate receptors; pharmacology; structural biology.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Brain / growth & development
  • Brain / metabolism
  • Humans
  • Ligand-Gated Ion Channels / chemistry
  • Ligand-Gated Ion Channels / metabolism
  • Protein Conformation
  • Receptors, AMPA / chemistry*
  • Receptors, AMPA / metabolism
  • Receptors, Ionotropic Glutamate / chemistry*
  • Receptors, Ionotropic Glutamate / metabolism
  • Receptors, Kainic Acid / chemistry*
  • Receptors, Kainic Acid / metabolism
  • Receptors, N-Methyl-D-Aspartate / chemistry*
  • Receptors, N-Methyl-D-Aspartate / metabolism
  • Structure-Activity Relationship
  • Synaptic Transmission / genetics

Substances

  • Ligand-Gated Ion Channels
  • Receptors, AMPA
  • Receptors, Ionotropic Glutamate
  • Receptors, Kainic Acid
  • Receptors, N-Methyl-D-Aspartate