title: Functional identification of Gd3+ binding site of metabotropic glutamate receptor 1alpha.
abstract: We previously reported that the metabotropic glutamate receptor1alpha (mGluR1alpha) has a sensitivity to extracellular polyvalent cations such as Ca(2+) and Gd(3+) as well as glutamate. Gd(3+) binding site was recently identified by crystal structure analysis at the interface of two subunits including Glu238, but it remains unknown whether this site is functionally involved in the activation of mGluR1alpha by Gd(3+) or not. We analyzed the ligand sensitivity of the Glu238Gln mutant, and observed that the sensitivity to extracellular Gd(3+) was completely lost, while the sensitivity to glutamate and Ca(2+) was not affected. We also observed that the presence of Gd(3+) increased the sensitivity of mGluR1alpha to glutamate, and that this effect was again lost by Glu238Gln mutation. These results suggest that the binding of Gd(3+) or a related endogenous substance to this site, alone or in cooperation with glutamate binding at a distant site, leads mGluR1alpha to activation.
authors.affiliation: Department of Physiology and Cell Biology, Tokyo Medical and Dental University, Graduate School and Faculty of Medicine, D-566, 1-5-45 Yushima, Bunkyo, Tokyo 113-8519, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Abe
authors.forename: Michihiro
authors.initials: M
authors.lastname: Tateyama
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kubo
mesh_terms: D001665:Binding Sites; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D005682:Gadolinium / Q000737:chemistry*; D018698:Glutamic Acid / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D017354:Point Mutation; D017434:Protein Structure, Tertiary; D018094:Receptors, Metabotropic Glutamate / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*
chemical_list: D008024:Ligands; D018094:Receptors, Metabotropic Glutamate; D018698:Glutamic Acid; D005682:Gadolinium; D002118:Calcium