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Functional identification of Gd 3+ binding site of metabotropic glutamate receptor 1α
Author(s) -
Abe Hideki,
Tateyama Michihiro,
Kubo Yoshihiro
Publication year - 2003
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(03)00569-6
Subject(s) - metabotropic glutamate receptor 1 , metabotropic glutamate receptor , glutamate receptor , metabotropic glutamate receptor 5 , chemistry , metabotropic receptor , binding site , metabotropic glutamate receptor 6 , metabotropic glutamate receptor 2 , biochemistry , extracellular , biophysics , stereochemistry , biology , receptor
We previously reported that the metabotropic glutamate receptor1α (mGluR1α) 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 mGluR1α 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 mGluR1α 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 mGluR1α to activation.