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GPCR二聚体别构调节的药理学作用 被引量：3

The Pharmacological Effect of Allosteric Regulation at GPCR Heterodimer
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摘要 传统的观点认为G蛋白偶联受体(G protein coupled receptor,GPCR)主要以单体形式存在,其作用是线性的,即配体结合到正位作用位点来引起信号下游传导。但大量事实证明,GPCR也能以同源或异源二聚体的形式存在。在二聚体中,由于配体结合到二聚体中的一个单体而引起对另一个单体的别构调节,从而形成别构位点,使受体的信号途径发生改变,引起一系列功能变化。别构调节剂与传统的激动剂相比有许多优点,因此是重要的GPCR靶标的候选药物。本文就GPCR二聚体的别构调节对受体功能的影响,以及筛选GPCR二聚体别构药物的技术做一简要综述,从而有助于GPCR药物的开发和利用。 Traditionally GPCR can exist as monomer,and its function is linear.The signal is transduced when the ligand binds to the orthosteric site.It has been reported that GPCR can form homodimer or heterodimer.In the dimers,allosteric sites will form when ligand binds to one monomer and then regulates of another monomer.Therefore the signaling pathway and the function of the receptor will be changed.Compared to orthosteric agonists,allosteric modulators have a number of potential advantages,which make allosteric modulators as a drug discovery candidate for GPCR.Herein,we introduce the concept of allosteric regulation at GPCR dimers,and its impact on the function of the receptor.We also introduce the drug screening methods of allosteric regulator,and those will contribute to drug discovery for GPCR.
作者 张宁 陈京 龚磊 刘路路 白波
机构地区 曲阜师范大学生命科学学院 济宁医学院神经生物学研究所
出处 《生理科学进展》 CAS CSCD 北大核心 2013年第2期93-98,共6页 Progress in Physiological Sciences
基金 国家自然科学基金(30971081 81070961) 山东省自然科学基金(ZR2011CM027 ZR2009DZ004) 山东省泰山学者建设工程专项经费资助课题
关键词 G蛋白偶联受体 二聚体 别构调节 药物筛选 共振能量转移 G protein coupled receptor dimer allosteric regulation drug screening resonance energy transfer
分类号 R05 [医药卫生] R329 [医药卫生—人体解剖和组织胚胎学]
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参考文献25

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二级参考文献15

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生理科学进展
2013年 第2期

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