Functional identification of Gd3+ binding site of metabotropic glutamate receptor 1α

FEBS Letters

Abe, Hideki¹  Kubo, Yoshihiro¹  Tateyama, Michihiro¹ 

[1] 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

关键词: Metabotropic glutamate receptor;    Ca2+;    Gd3+;    Structure function;    Polyamine;    mGluR1α;    metabotropic glutamate receptor1α;    [Ca2+]o;    extracellular Ca2+;    [Gd3+]o;    extracellular Gd3+;    [Ca2+]i;    intracellular Ca2+;    w.t.;    wild type;    CSF;    cerebro spinal fluid;   

DOI  :  10.1016/S0014-5793(03)00569-6

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

We previously reported that the metabotropic glutamate receptor1α (mGluR1α) has a sensitivity to extracellular polyvalent cations such as Ca²⁺ and Gd³⁺ as well as glutamate. Gd³⁺ 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 Gd³⁺ or not. We analyzed the ligand sensitivity of the Glu238Gln mutant, and observed that the sensitivity to extracellular Gd³⁺ was completely lost, while the sensitivity to glutamate and Ca²⁺ was not affected. We also observed that the presence of Gd³⁺ increased the sensitivity of mGluR1α to glutamate, and that this effect was again lost by Glu238Gln mutation. These results suggest that the binding of Gd³⁺ or a related endogenous substance to this site, alone or in cooperation with glutamate binding at a distant site, leads mGluR1α to activation.

【 授权许可】

Unknown