Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Identification of an extracellular motif involved in the binding of guanine nucleotides by a glutamate receptor.
Paas Y
,
Devillers-Thiéry A
,
Changeux JP
,
Medevielle F
,
Teichberg VI
.
???displayArticle.abstract???
The chick cerebellar kainate (KA) binding protein (KBP), a member of the family of ionotropic glutamate receptors, harbours a glycine-rich (GxGxxG) motif known to be involved in the binding of ATP and GTP to kinases and G proteins respectively. Here, we report that guanine, but not adenine, nucleotides interact with KBP by inhibiting [3H]KA binding in a competitive-like manner, displaying IC50 values in the micromolar range. To locate the GTP binding site, KBP was photoaffinity labelled with [alpha-32P]GTP. The reaction was blocked by KA, glutamate, 6-cyano-7-nitroquinoxaline-2,3-dione and antibodies raised against a peptide containing the glycine-rich motif. Site-directed mutagenesis of residues K72 and Y73 within the glycine-rich motif followed by the expression of the KBP mutants at the surface of HEK 293 cells showed a decrease in GTP binding affinity by factors of 10 and 100 respectively. The binding of [3H]KA to the K72A/T KBP mutants was not affected but binding to the Y73I KBP mutant was decreased by a factor of 10. Accordingly, we propose that the glycine-rich motif of KBP forms part of a guanine nucleotide binding site. We further suggest that the glycine-rich motif is the binding site at which guanine nucleotides inhibit the glutamate-mediated responses of various members of the subfamily of glutamate ionotropic receptors.
Baron,
Guanine nucleotides are competitive inhibitors of N-methyl-D-aspartate at its receptor site both in vitro and in vivo.
1989, Pubmed
Baron,
Guanine nucleotides are competitive inhibitors of N-methyl-D-aspartate at its receptor site both in vitro and in vivo.
1989,
Pubmed
Bennett,
Topology profile for a glutamate receptor: three transmembrane domains and a channel-lining reentrant membrane loop.
1995,
Pubmed
,
Xenbase
Berchtold,
Crystal structure of active elongation factor Tu reveals major domain rearrangements.
1993,
Pubmed
Bettler,
Cloning of a novel glutamate receptor subunit, GluR5: expression in the nervous system during development.
1990,
Pubmed
,
Xenbase
Bettler,
Cloning of a putative glutamate receptor: a low affinity kainate-binding subunit.
1992,
Pubmed
,
Xenbase
Boulter,
Molecular cloning and functional expression of glutamate receptor subunit genes.
1990,
Pubmed
,
Xenbase
Bourne,
The GTPase superfamily: conserved structure and molecular mechanism.
1991,
Pubmed
Budson,
GDP beta S antagonizes whole-cell current responses to excitatory amino acids.
1991,
Pubmed
Chen,
High-efficiency transformation of mammalian cells by plasmid DNA.
1987,
Pubmed
Choi,
Bench to bedside: the glutamate connection.
1992,
Pubmed
Choi,
Glutamate neurotoxicity and diseases of the nervous system.
1988,
Pubmed
Egebjerg,
Cloning of a cDNA for a glutamate receptor subunit activated by kainate but not AMPA.
1991,
Pubmed
,
Xenbase
Gallo,
Molecular cloning and development analysis of a new glutamate receptor subunit isoform in cerebellum.
1992,
Pubmed
,
Xenbase
Gilman,
G proteins: transducers of receptor-generated signals.
1987,
Pubmed
Gorodinsky,
A ligand binding study of the interactions of guanine nucleotides with non-NMDA receptors.
1993,
Pubmed
Gregor,
Molecular structure of the chick cerebellar kainate-binding subunit of a putative glutamate receptor.
1989,
Pubmed
Gregor,
Isolation, immunochemical characterization and localization of the kainate sub-class of glutamate receptor from chick cerebellum.
1988,
Pubmed
Herb,
The KA-2 subunit of excitatory amino acid receptors shows widespread expression in brain and forms ion channels with distantly related subunits.
1992,
Pubmed
Higashijima,
Effects of Mg2+ and the beta gamma-subunit complex on the interactions of guanine nucleotides with G proteins.
1987,
Pubmed
Higashijima,
The effect of GTP and Mg2+ on the GTPase activity and the fluorescent properties of Go.
1987,
Pubmed
Hollmann,
Cloning by functional expression of a member of the glutamate receptor family.
1989,
Pubmed
,
Xenbase
Hollmann,
Cloned glutamate receptors.
1994,
Pubmed
Hollmann,
N-glycosylation site tagging suggests a three transmembrane domain topology for the glutamate receptor GluR1.
1994,
Pubmed
,
Xenbase
Hood,
Guanine nucleotide modulation of [3H]TCP binding to the NMDA receptor complex.
1990,
Pubmed
Keinänen,
A family of AMPA-selective glutamate receptors.
1990,
Pubmed
Kuryatov,
Mutational analysis of the glycine-binding site of the NMDA receptor: structural similarity with bacterial amino acid-binding proteins.
1994,
Pubmed
,
Xenbase
Li,
Functional effects of mutations in the putative agonist binding region of recombinant alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors.
1995,
Pubmed
,
Xenbase
Molnár,
Membrane topology of the GluR1 glutamate receptor subunit: epitope mapping by site-directed antipeptide antibodies.
1994,
Pubmed
Molnár,
Biochemical and immunocytochemical characterization of antipeptide antibodies to a cloned GluR1 glutamate receptor subunit: cellular and subcellular distribution in the rat forebrain.
1993,
Pubmed
Monaghan,
The excitatory amino acid receptors: their classes, pharmacology, and distinct properties in the function of the central nervous system.
1989,
Pubmed
Moriyoshi,
Molecular cloning and characterization of the rat NMDA receptor.
1991,
Pubmed
,
Xenbase
Munson,
Ligand: a versatile computerized approach for characterization of ligand-binding systems.
1980,
Pubmed
Noel,
The 2.2 A crystal structure of transducin-alpha complexed with GTP gamma S.
1993,
Pubmed
Pai,
Structure of the guanine-nucleotide-binding domain of the Ha-ras oncogene product p21 in the triphosphate conformation.
1989,
Pubmed
Pai,
Refined crystal structure of the triphosphate conformation of H-ras p21 at 1.35 A resolution: implications for the mechanism of GTP hydrolysis.
1990,
Pubmed
Saraste,
The P-loop--a common motif in ATP- and GTP-binding proteins.
1990,
Pubmed
Schuster,
Molecular cloning of an invertebrate glutamate receptor subunit expressed in Drosophila muscle.
1991,
Pubmed
,
Xenbase
Sharif,
Regulation of cerebellar L-[3H]glutamate binding: influence of guanine nucleotides and Na+ ions.
1981,
Pubmed
Stern-Bach,
Agonist selectivity of glutamate receptors is specified by two domains structurally related to bacterial amino acid-binding proteins.
1994,
Pubmed
,
Xenbase
Swick,
Promoter-cDNA-directed heterologous protein expression in Xenopus laevis oocytes.
1992,
Pubmed
,
Xenbase
Taylor,
The role of G proteins in transmembrane signalling.
1990,
Pubmed
Towbin,
Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications.
1979,
Pubmed
Uchino,
Mutations in a putative agonist binding region of the AMPA-selective glutamate receptor channel.
1992,
Pubmed
,
Xenbase
Ultsch,
Glutamate receptors of Drosophila melanogaster: cloning of a kainate-selective subunit expressed in the central nervous system.
1992,
Pubmed
,
Xenbase
Wada,
Sequence and expression of a frog brain complementary DNA encoding a kainate-binding protein.
1989,
Pubmed
Wafford,
Identification of amino acids in the N-methyl-D-aspartate receptor NR1 subunit that contribute to the glycine binding site.
1995,
Pubmed
,
Xenbase
Werner,
Cloning of a putative high-affinity kainate receptor expressed predominantly in hippocampal CA3 cells.
1991,
Pubmed
Wierenga,
Predicted nucleotide-binding properties of p21 protein and its cancer-associated variant.
1983,
Pubmed
Willard,
The interaction of a kainate receptor from goldfish brain with a pertussis toxin-sensitive GTP-binding protein.
1991,
Pubmed
Willard,
Interaction of the frog brain kainate receptor expressed in Chinese hamster ovary cells with a GTP-binding protein.
1992,
Pubmed
Ziegra,
Coupling of a purified goldfish brain kainate receptor with a pertussis toxin-sensitive G protein.
1992,
Pubmed
Zimmermann,
Signalling via ATP in the nervous system.
1994,
Pubmed
