Closed state of both binding domains of homodimeric mGlu receptors is required for full activity
Closed state of both binding domains of homodimeric mGlu receptors is required for full activity
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DOI：
10.1038/nsmb794
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发表时间：
2004-08-01
影响因子：
16.8
通讯作者：
Pin, JP
中科院分区：
文献类型：
--
作者：
Kniazeff, J;Bessis, AS;Pin, JP
膜受体是信号转导的关键成分，通常起二聚体的作用。这些包括一些G蛋白偶联受体，如代谢性谷氨酸(MGlu)受体，它们有大的胞外结构域(ECDs)，激动剂与之结合。二聚体ECDs中的激动剂结合如何激活效应域在很大程度上仍不清楚。在激动剂存在的情况下，mGlu(1)的二聚体ECDs的结构显示出两种特定的构象，其中一个或两个原基都处于激动剂稳定的闭合状态。在这里，我们检查了这两种构象是否对应于全长受体的一种活性形式。使用一个允许形成由野生型和突变型亚基组成的二聚体的系统，我们证明了每个二聚体关闭一个ECD就足以激活受体，但关闭两个ECDs才能完全激活。
Membrane receptors, key components in signal transduction, often function as dimers. These include some G protein - coupled receptors such as metabotropic glutamate ( mGlu) receptors that have large extracellular domains (ECDs) where agonists bind. How agonist binding in dimeric ECDs activates the effector domains remains largely unknown. The structure of the dimeric ECDs of mGlu(1) solved in the presence of agonist revealed two specific conformations in which either one or both protomers are in an agonist-stabilized closed form. Here we examined whether both conformations correspond to an active form of the full-length receptor. Using a system that allows the formation of dimers made of a wild-type and a mutant subunit, we show that the closure of one ECD per dimer is sufficient to activate the receptor, but the closure of both ECDs is required for full activity.