A single tryptophan on M2 of glutamate receptor channels confers high permeability to divalent cations.
A single tryptophan on M2 of glutamate receptor channels confers high permeability to divalent cations.
复制标题
谷氨酸受体通道 M2 上的单个色氨酸赋予二价阳离子高渗透性。
DOI：
10.1016/s0006-3495(96)79274-3
复制
发表时间：
1996
影响因子：
3.4
通讯作者：
Montal,M
中科院分区：
文献类型：
--
作者：
Ferrer-Montiel,AV;Sun,W;Montal,M
α-氨基-3-羟基-5-甲基-4-异恶唑丙酸盐/红藻氨酸盐亚型的离子型谷氨酸受体（iGluR）显示出比N-甲基-D-天冬氨酸（NMDA）亚型更低的Ca 2+渗透性。M2跨膜段（M2）上的N/Q/R位点是非NMDA受体亚家族成员表现出的不同Ca 2+渗透性的重要决定因素。然而，这个网站，并不完全占不同的渗透性能显示的非NMDA和NMDA受体，这表明其他分子的决定因素的参与。我们已经确定了α-氨基-3-羟基-5-甲基-4-异恶唑丙酸盐/红藻氨酸盐受体GluR 1的M2上的其他分子元素，这些分子元素指定了其渗透特性。通过位置577处的色氨酸赋予GluR 1对二价阳离子比一价阳离子更高的渗透性，而通过位置582处的天冬酰胺赋予外部二价阳离子的阻断。因此，离子型谷氨酸受体的渗透特性似乎主要由M2上的两个不同的决定因素，即众所周知的N/Q/R位点和新发现的L/W位点来指定。这些发现证实了M2是孔隙内衬的结构组分的概念。
Ionotropic glutamate receptors (iGluRs) of the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate/kainate subtype display lower permeability to Ca2+ than the N-methyl-D-aspartate (NMDA) subtype. The well-documented N/Q/R site on the M2 transmembrane segment (M2) is an important determinant of the distinct Ca2+ permeability exhibited by members of the non-NMDA receptor subfamily. This site, however, does not completely account for the different permeation properties displayed by non-NMDA and NMDA receptors, suggesting the involvement of other molecular determinants. We have identified additional molecular elements on M2 of the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate/kainate receptor GluR1 that specify its permeation properties. Higher permeability to divalent over monovalent cations is conferred on GluR1 by a tryptophan at position 577, whereas blockade by external divalent cations is imparted by an asparagine at position 582. Hence, the permeation properties of ionotropic glutamate receptors appear to be primarily specified by two distinct determinants on M2, the well-known N/Q/R site and the newly identified L/W site. These findings substantiate the notion that M2 is a structural component of the pore lining.