title: Radial symmetry in a chimeric glutamate receptor pore.
abstract: Ionotropic glutamate receptors comprise two conformationally different A/C and B/D subunit pairs. Closed channels exhibit fourfold radial symmetry in the transmembrane domain (TMD) but transition to twofold dimer-of-dimers symmetry for extracellular ligand binding and N-terminal domains. Here, to evaluate symmetry in open pores we analysed interaction between the Q/R editing site near the pore loop apex and the transmembrane M3 helix of kainate receptor subunit GluK2. Chimeric subunits that combined the GluK2 TMD with extracellular segments from NMDA receptors, which are obligate heteromers, yielded channels made up of A/C and B/D subunit pairs with distinct substitutions along M3 and/or Q/R site editing status, in an otherwise identical homotetrameric TMD. Our results indicate that Q/R site interaction with M3 occurs within individual subunits and is essentially the same for both A/C and B/D subunit conformations, suggesting that fourfold pore symmetry persists in the open state.
authors.affiliation: Department of Cell Biology and Physiology, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, Missouri 63110, USA.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Wilding
authors.affiliation: Department of Cell Biology and Physiology, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, Missouri 63110, USA.
authors.forename: Melany N
authors.initials: MN
authors.lastname: Lopez
authors.affiliation: Department of Cell Biology and Physiology, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, Missouri 63110, USA.
authors.forename: James E
authors.initials: JE
authors.lastname: Huettner
mesh_terms: D000595:Amino Acid Sequence; D018076:DNA, Complementary / Q000378:metabolism*; D004281:Docosahexaenoic Acids / Q000378:metabolism; D004594:Electrophysiology; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D058468:Receptors, Ionotropic Glutamate / Q000737:chemistry / Q000378:metabolism*; D018092:Kainic Acid Receptors / Q000737:chemistry / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000737:chemistry / Q000378:metabolism
chemical_list: D018076:DNA, Complementary; D004281:Docosahexaenoic Acids; D058468:Receptors, Ionotropic Glutamate; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate