Amino terminal domains of the NMDA receptor are organized as local heterodimers.
Amino terminal domains of the NMDA receptor are organized as local heterodimers.
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DOI：
10.1371/journal.pone.0019180
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发表时间：
2011-04-22
期刊：
影响因子：
3.7
通讯作者：
Gouaux E
中科院分区：
文献类型：
--
作者：
Lee CH;Gouaux E
N-甲基-D-天冬氨酸（NMDA）受体是一种专性异源四聚体组装体，由两个甘氨酸结合GluN 1亚基和两个谷氨酸结合GluN 2亚基组成。尽管NMDA受体在神经系统中起着至关重要的作用，但在二聚体的二聚体组合中亚基的具体排列并不完全清楚。在这里，我们研究了组织的氨基末端结构域（ATD）的大鼠GluN 1/GluN 2A和GluN 1/GluN 2B NMDA受体的半胱氨酸指导，二硫键介导的交联。我们发现，GluN 1 ATDs和GluN 2 ATDs自发形成二硫键介导的二聚体后，引入半胱氨酸到L1接口的GluN 2A或GluN 2B ATD。二聚体的形成可以通过敲除位于GluN 1的L1界面附近的内源性半胱氨酸来防止。这些结果表明，GluN 1和GluN 2 ATDs通过L1-L1界面的相互作用形成局部异源二聚体，并进一步证明了GluN 1/GluN 2A和GluN 1/GluN 2B NMDA受体的异源二聚体排列。
The N-methyl-D-aspartate (NMDA) receptor, an obligate heterotetrameric assembly organized as a dimer of dimers, is typically composed of two glycine-binding GluN1 subunits and two glutamate-binding GluN2 subunits. Despite the crucial role that the NMDA receptor plays in the nervous system, the specific arrangement of subunits within the dimer-of-dimer assemblage is not conclusively known. Here we studied the organization of the amino terminal domain (ATD) of the rat GluN1/GluN2A and GluN1/GluN2B NMDA receptors by cysteine-directed, disulfide bond-mediated cross-linking. We found that GluN1 ATDs and GluN2 ATDs spontaneously formed disulfide bond-mediated dimers after introducing cysteines into the L1 interface of GluN2A or GluN2B ATD. The formation of dimer could be prevented by knocking out endogenous cysteines located near the L1 interface of GluN1. These results indicate that GluN1 and GluN2 ATDs form local heterodimers through the interactions in the L1-L1 interface and further demonstrate a dimer-of-heterodimer arrangement in GluN1/GluN2A and GluN1/GluN2B NMDA receptors.
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