NMDAR channel segments forming the extracellular vestibule inferred from the accessibility of substituted cysteines
NMDAR channel segments forming the extracellular vestibule inferred from the accessibility of substituted cysteines
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DOI：
10.1016/s0896-6273(00)80710-2
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发表时间：
1999-03-01
期刊：
影响因子：
16.2
通讯作者：
Kuner, T
中科院分区：
文献类型：
--
作者：
Beck, C;Wollmuth, LP;Kuner, T
在NMDA受体通道中，M2环形成狭窄的收缩和细胞质前庭。导致缩窄的细胞外前庭的身份仍然没有得到解决。使用取代的半胱氨酸可及性方法（SCAM），我们确定了NR 1亚基在M1之前区域（preM 1）、M3的C-末端部分（M3（C））和M4的N-末端部分（M4，）中的通道衬里残基。这些残基位于缩窄部的细胞外侧，并且除了一个例外，暴露于孔而不依赖于通道激活，这表明门在缩窄部或更远的胞质处。Ca 2+离子的渗透通过M3（C）和M4（N）中的突变而降低，但不通过preM 1中的突变，提示功能上不同的贡献的片段的细胞外前庭的NMDA受体通道。
In NMDA receptor channels, the M2 loop forms the narrow constriction and the cytoplasmic vestibule. The identity of an extracellular vestibule leading toward the constriction remained unresolved. Using the substituted cysteine accessibility method (SCAM), we identified channel-lining residues of the NR1 subunit in the region preceding M1 (preM1), the C-terminal part of M3 (M3(C)), and the N-terminal part of M4 (M4,). These residues are located on the extracellular side of the constriction and, with one exception, are exposed to the pore independently of channel activation, suggesting that the gate is at the constriction or further cytoplasmic to it. Permeation of Ca2+ ions was decreased by mutations in M3(C) and M4(N), but not by mutations in preM1, suggesting a functionally distinct contribution of the segments to the extracellular vestibule of the NMDA receptor channel.