Zou Juan, Jiang Jason Y, Yang Jenny J
Department of Chemistry, Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA 30303, USA.
Int J Mol Sci. 2017 Mar 21;18(3):672. doi: 10.3390/ijms18030672.
Metabotropic glutamate receptors (mGluRs) associated with the slow phase of the glutamatergic signaling pathway in neurons of the central nervous system have gained importance as drug targets for chronic neurodegenerative diseases. While extracellular Ca was reported to exhibit direct activation and modulation via an allosteric site, the identification of those binding sites was challenged by weak binding. Herein, we review the discovery of extracellular Ca in regulation of mGluRs, summarize the recent developments in probing Ca binding and its co-regulation of the receptor based on structural and biochemical analysis, and discuss the molecular basis for Ca to regulate various classes of drug action as well as its importance as an allosteric modulator in mGluRs.
与中枢神经系统神经元中谷氨酸能信号通路慢相相关的代谢型谷氨酸受体（mGluRs），作为慢性神经退行性疾病的药物靶点已变得越发重要。虽然据报道细胞外钙可通过变构位点表现出直接激活和调节作用，但这些结合位点的鉴定受到弱结合的挑战。在此，我们回顾细胞外钙在mGluRs调节中的发现，基于结构和生化分析总结在探测钙结合及其对受体的协同调节方面的最新进展，并讨论钙调节各类药物作用的分子基础及其作为mGluRs变构调节剂的重要性。
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