A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
AMPA receptors and bacterial periplasmic amino acid-binding proteins share the ionic mechanism of ligand recognition
Tekijät: Lampinen M, Pentikainen O, Johnson MS, Keinanen K
Kustantaja: OXFORD UNIV PRESS
Julkaisuvuosi: 1998
Journal: EMBO Journal
Tietokannassa oleva lehden nimi: EMBO JOURNAL
Lehden akronyymi: EMBO J
Vuosikerta: 17
Numero: 16
Aloitussivu: 4704
Lopetussivu: 4711
Sivujen määrä: 8
ISSN: 0261-4189
DOI: https://doi.org/10.1093/emboj/17.16.4704
Tiivistelmä
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 [H-3]AMPA-binding properties of the mutated binding sites, we constructed a revised three-dimensional model of the ligand-binding site, different in many respects from previously published models. In particular, our results indicate that the residues Arg507 and Glu727 represent the structural and functional correlates of Arg77 and Asp161 in the homologous bacterial lysine/ornithine/arginine-binding protein and histidine-binding protein, and directly interact with the alpha-carboxyl and alpha-amino group of the bound ligand, respectively. In contrast, Glu424, implicated previously in ionic interactions with the a-amino group of the agonist, is unlikely to have such a role in ligand binding. Our results indicate that glutamate receptors share with the bacterial polar amino acid-binding proteins the fundamental mechanism of amino acid 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 [H-3]AMPA-binding properties of the mutated binding sites, we constructed a revised three-dimensional model of the ligand-binding site, different in many respects from previously published models. In particular, our results indicate that the residues Arg507 and Glu727 represent the structural and functional correlates of Arg77 and Asp161 in the homologous bacterial lysine/ornithine/arginine-binding protein and histidine-binding protein, and directly interact with the alpha-carboxyl and alpha-amino group of the bound ligand, respectively. In contrast, Glu424, implicated previously in ionic interactions with the a-amino group of the agonist, is unlikely to have such a role in ligand binding. Our results indicate that glutamate receptors share with the bacterial polar amino acid-binding proteins the fundamental mechanism of amino acid recognition.
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