Hirai, H. ; Kirsch, J. ; Laube, Bodo ; Betz, H. ; Kuhse, J. (1996)
The glycine binding site of the N-methyl-D-aspartate receptor subunit NR1: identification of novel determinants of co-agonist potentiation in the extracellular M3-M4 loop region.
In: Proceedings of the National Academy of Sciences of the United States of America, 93 (12)
Artikel, Bibliographie
Kurzbeschreibung (Abstract)
The N-methyl-D-aspartate (NMDA) subtype of ionotropic glutamate receptors is a heterooligomeric membrane protein composed of homologous subunits. Here, the contribution of the M3-M4 loop of the NR1 subunit to the binding of glutamate and the co-agonist glycine was investigated by site-directed mutagenesis. Substitution of the phenylalanine residues at positions 735 or 736 of the M3-M4 loop produced a 15- to 30-fold reduction in apparent glycine affinity without affecting the binding of glutamate and the competitive glycine antagonist 7-chlorokynurenic acid; mutation of both residues caused a >100-fold decrease in glycine affinity. These residues are found in a C-terminal region of the M3-M4 loop that shows significant sequence similarity to bacterial amino acid-binding proteins. Epitope tagging revealed both the N-terminus and the M3-M4 loop to be exposed extracellularly, whereas a C-terminal epitope was localized intracellularly. These results indicate that the M3-M4 loop is part of the ligand-binding pocket of the NR1 subunit and provide the basis for a refined model of the glycine-binding site of the NMDA receptor.
| Typ des Eintrags: | Artikel |
|---|---|
| Erschienen: | 1996 |
| Autor(en): | Hirai, H. ; Kirsch, J. ; Laube, Bodo ; Betz, H. ; Kuhse, J. |
| Art des Eintrags: | Bibliographie |
| Titel: | The glycine binding site of the N-methyl-D-aspartate receptor subunit NR1: identification of novel determinants of co-agonist potentiation in the extracellular M3-M4 loop region. |
| Sprache: | Englisch |
| Publikationsjahr: | 1996 |
| Titel der Zeitschrift, Zeitung oder Schriftenreihe: | Proceedings of the National Academy of Sciences of the United States of America |
| Jahrgang/Volume einer Zeitschrift: | 93 |
| (Heft-)Nummer: | 12 |
| Kurzbeschreibung (Abstract): | The N-methyl-D-aspartate (NMDA) subtype of ionotropic glutamate receptors is a heterooligomeric membrane protein composed of homologous subunits. Here, the contribution of the M3-M4 loop of the NR1 subunit to the binding of glutamate and the co-agonist glycine was investigated by site-directed mutagenesis. Substitution of the phenylalanine residues at positions 735 or 736 of the M3-M4 loop produced a 15- to 30-fold reduction in apparent glycine affinity without affecting the binding of glutamate and the competitive glycine antagonist 7-chlorokynurenic acid; mutation of both residues caused a >100-fold decrease in glycine affinity. These residues are found in a C-terminal region of the M3-M4 loop that shows significant sequence similarity to bacterial amino acid-binding proteins. Epitope tagging revealed both the N-terminus and the M3-M4 loop to be exposed extracellularly, whereas a C-terminal epitope was localized intracellularly. These results indicate that the M3-M4 loop is part of the ligand-binding pocket of the NR1 subunit and provide the basis for a refined model of the glycine-binding site of the NMDA receptor. |
| Fachbereich(e)/-gebiet(e): | 10 Fachbereich Biologie 10 Fachbereich Biologie > Neurophysiologie und neurosensorische Systeme ?? fb10_zoologie ?? |
| Hinterlegungsdatum: | 12 Apr 2011 09:36 |
| Letzte Änderung: | 05 Mär 2019 06:48 |
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