The NMDA receptor M3 segment is a conserved transduction element coupling ligand binding to channel opening
The NMDA receptor M3 segment is a conserved transduction element coupling ligand binding to channel opening
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DOI：
10.1523/jneurosci.22-06-02044.2002
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发表时间：
2002-03-15
影响因子：
5.3
通讯作者：
VanDongen, AMJ
中科院分区：
文献类型：
--
作者：
Jones, KS;VanDongen, HMA;VanDongen, AMJ
离子通道在打开和关闭两种功能状态之间随机交替。这种门控行为分别由膜电位或电压门控通道和配体门控通道中神经递质的结合控制。尽管在确定配体结合核心和电压传感器的结构和功能方面已经取得了很大进展，但这些结构域如何耦合到通道开放仍然知之甚少。在这里，我们证明了NMDA受体的M3跨膜片段与配体结合核心和通道门都是变构相互作用的。有人认为，M3作为一种转导元件，其构象变化将配体结合与通道开放结合在一起。此外，K+通道中谷氨酸受体M3片段与相应的S6或TM2片段之间的氨基酸同源性表明，离子通道的激活和门控在结构和功能上都是保守的。
Ion channels alternate stochastically between two functional states, open and closed. This gating behavior is controlled by membrane potential or by the binding of neurotransmitters in voltage- and ligand-gated channels, respectively. Although much progress has been made in defining the structure and function of the ligand-binding cores and the voltage sensors, how these domains couple to channel opening remains poorly understood. Here we show that the M3 transmembrane segments of the NMDA receptor allosterically interact with both the ligand-binding cores and the channel gate. It is proposed that M3 functions as a transduction element whose conformational change couples ligand binding with channel opening. Furthermore, amino acid homology between glutamate receptor M3 segments and the equivalent S6 or TM2 segments in K+ channels suggests that ion channel activation and gating are both structurally and functionally conserved.