Structure and symmetry inform gating principles of ionotropic glutamate receptors.
Ionotropic glutamate receptors (iGluRs) transduce signals derived from release of the excitatory neurotransmitter glutamate from pre-synaptic neurons into excitation of post-synaptic neurons on a millisecond time-scale. In recent years, the elucidation of full-length iGluR structures of NMDA, AMPA and kainate receptors by X-ray crystallography and single particle cryo-electron microscopy has greatly enhanced our understanding of the interrelationships between receptor architecture and gating mechanism. Here we briefly review full-length iGluR structures and discuss the similarities and differences between NMDA receptors and non-NMDA iGluRs. We focus on distinct conformations, including ligand-free, agonist-bound active, agonist-bound desensitized and antagonist-bound conformations as well as modulator and auxiliary protein-bound states. These findings provide insights into structure-based mechanisms of iGluR gating and modulation which together shape the amplitude and time course of the excitatory postsynaptic potential. This article is part of the Special Issue entitled 'Ionotropic glutamate receptors'.
Vollum Institute, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland OR 97239, USA.
Shujia
S
Zhu
Vollum Institute, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland OR 97239, USA; Howard Hughes Medical Institute, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland OR 97239, USA. Electronic address: gouauxe@ohsu.edu.
Eric
E
Gouaux
D000818:Animals; D001665:Binding Sites; D018360:Crystallography, X-Ray; D006801:Humans; D015640:Ion Channel Gating; D008958:Models, Molecular; D011487:Protein Conformation; D018091:Receptors, AMPA / Q000737:chemistry / Q000502:physiology; D058468:Receptors, Ionotropic Glutamate / Q000737:chemistry* / Q000502:physiology*; D018092:Kainic Acid Receptors / Q000737:chemistry / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000737:chemistry / Q000502:physiology
D018091:Receptors, AMPA; D058468:Receptors, Ionotropic Glutamate; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate
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