Krupp J J, Vissel B, Heinemann S F, Westbrook G L
Vollum Institute, Oregon Health Sciences University, Portland 97201, USA.
Neuron. 1998 Feb;20(2):317-27. doi: 10.1016/s0896-6273(00)80459-6.
Recent molecular studies of glutamate channels have provided increasingly detailed models of the agonist-binding site and of the channel pore. However, little information is available on the domains involved in channel gating. We examined the molecular determinants for the NR2-subunit specificity of glycine-independent desensitization of NMDA channels using NR2C/NR2A chimeric subunits expressed in HEK 293 cells. We show that glycine-independent desensitization is controlled by N-terminal domains of the NR2 subunit that flank the putative agonist-binding domain: a four amino acid (aa) segment immediately preceding the first transmembrane domain (M1) and a region containing the leucine/isoleucine/valine-binding protein-like (LIVBP-like) domain. Our results provide evidence for a functional role of the region containing the LIVBP-like domain in glutamate receptor channels. We suggest that the pre-M1 segment, presumably situated near the entrance to the pore, serves as a dynamic link between ligand binding and channel gating.
近期对谷氨酸通道的分子研究为激动剂结合位点和通道孔提供了越来越详细的模型。然而，关于参与通道门控的结构域的信息却很少。我们使用在HEK 293细胞中表达的NR2C/NR2A嵌合亚基，研究了NMDA通道甘氨酸非依赖性脱敏的NR2亚基特异性的分子决定因素。我们发现，甘氨酸非依赖性脱敏由NR2亚基的N端结构域控制，这些结构域位于假定的激动剂结合结构域两侧：紧接第一个跨膜结构域（M1）之前的一个四氨基酸（aa）片段，以及一个包含亮氨酸/异亮氨酸/缬氨酸结合蛋白样（LIVBP样）结构域的区域。我们的结果为包含LIVBP样结构域的区域在谷氨酸受体通道中的功能作用提供了证据。我们认为，M1前的片段可能位于孔的入口附近，作为配体结合和通道门控之间的动态连接。
