AMPA receptor ligand-binding domain: Site-directed mutagenesis study of ligand-receptor interactions

نویسندگان

  • Milla Lampinen
  • Kari Keinänen
  • Kristiina Takkinen
  • Ulla Petäjä-Repo
  • Karl Åkerman
چکیده

Academic Dissertation To be presented for public criticism, with the permission of the Faculty of Science of the (1998) Disulfide bonding and cysteine accessibility in the α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor subunit GluRD. Implications for redox modulation of glutamate receptors. receptors and bacterial periplasmic amino acid-binding proteins share the ionic mechanism of ligand recognition. (2002) Discrimination between agonists and antagonists by the α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid-selective glutamate receptor. A mutation analysis of the ligand-binding domain of GluR-D subunit. Characterization of ligand-binding domains of GluR-B and GluR-D glutamate receptor subunits expressed as periplasmic proteins in Eschericia coli. ABBREVIATIONS AMPA α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid CAMKII Ca 2+-and calmodulin dependent protein kinase II CNS central nervous system CNQX 6-cyano-7-nitroquinoxaline-2,3-dione CTZ cyclothiazide DNQX 6,7-dinitroquinoxaline-2,3-dione DTNB 5,5´-dithiobis-(2-nitrobenzoic acid) DTT 4-dithio-DL-threitol EC 50 effective concentration EPSC excitatory postsynaptic current EPSP excitatory postsynaptic potential GABA γ-aminobutyric acid GlnBP glutamine binding protein GRIP glutamate receptor-interacting protein HBP histidine binding protein HIBO homoibotenic acid iGluR ionotropic glutamate receptor KBP kainate-binding protein K i inhibition constant K d dissociation constant KSCN potassium thiocyanate LAOBP lysine/arginine/ornithine-binding protein LIVBP leucine-isoleucine-valine-binding proteins LTD long-term depression of synaptic strength LTP long-term potentiation of synaptic strength mGluR metabotropic glutamate receptor NMDA N-methyl-D-aspartate ODNB n-octyl-5-dithio-2-nitrobenzoic acid PAGE polyacrylamide gel electrophoresis PBP periplasmic amino acid binding protein PDZ PSD-95/blg/ZO-1 PEPA

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AMPA receptors and bacterial periplasmic amino acid-binding proteins share the ionic mechanism of ligand recognition.

In order to identify key structural determinants for ligand recognition, we subjected the ligand-binding domain of the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)-selective glutamate receptor GluR-D subunit to site-directed mutagenesis. Based on the analysis of the [3H]AMPA-binding properties of the mutated binding sites, we constructed a revised three-dimensional model of ...

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تاریخ انتشار 2003