title: Emerging models of glutamate receptor ion channel structure and function.
abstract: Excitatory synaptic transmission in the brain is mediated by ligand-gated ion channels (iGluRs) activated by glutamate. Distinct from other neurotransmitter receptors, the extracellular domains of iGluRs are loosely packed assemblies with two clearly distinct layers, each of which has both local and global 2-fold axes of symmetry. By contrast, the iGluR transmembrane segments have 4-fold symmetry and share a conserved pore loop architecture found in tetrameric voltage-gated ion channels. The striking layered architecture of iGluRs revealed by the 3.6 Å resolution structure of an AMPA receptor homotetramer likely arose from gene fusion events that occurred early in evolution. Although this modular design has greatly facilitated biophysical and structural studies on individual iGluR domains, and suggested conserved mechanisms for iGluR gating, recent work is beginning to reveal unanticipated diversity in the structure, allosteric regulation, and assembly of iGluR subtypes.
authors: Laboratory of Cellular and Molecular Neurophysiology, Porter Neuroscience Research Center, NICHD, NIH, DHHS, Bethesda, MD 20892, USA. mayerm@mail.nih.gov
authors: Mark L
authors: ML
authors: Mayer
mesh_terms: D000818:Animals; D001665:Binding Sites; D055592:Biophysical Phenomena; D018360:Crystallography, X-Ray; D018690:Excitatory Amino Acid Agonists / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D015640:Ion Channel Gating; D008024:Ligands; D008565:Membrane Proteins / Q000378:metabolism / Q000502:physiology; D008958:Models, Molecular; D009154:Mutation; D011487:Protein Conformation; D055503:Protein Multimerization; D051381:Rats; D058468:Receptors, Ionotropic Glutamate / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology*; D013329:Structure-Activity Relationship; D014981:Xenopus / Q000378:metabolism / Q000502:physiology; D029867:Xenopus Proteins / Q000378:metabolism
chemical_list: D018690:Excitatory Amino Acid Agonists; D008024:Ligands; D008565:Membrane Proteins; D058468:Receptors, Ionotropic Glutamate; D029867:Xenopus Proteins; D018698:Glutamic Acid