Gating at the selectivity filter in cyclic nucleotide-gated channels
Gating at the selectivity filter in cyclic nucleotide-gated channels
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DOI：
10.1073/pnas.0709809105
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发表时间：
2008-03-04
影响因子：
11.1
通讯作者：
Holmgren, Miguel
中科院分区：
文献类型：
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作者：
Contreras, Jorge E.;Srikumar, Deepa;Holmgren, Miguel
通过响应 cGMP 结合而打开和关闭渗透途径（门控），环核苷酸门控 (CNG) 通道在视觉和嗅觉信号的转导中发挥关键作用。汇编证据表明 CNG 通道中的激活门并不位于孔的细胞内末端，因为它是为电压激活的钾 (K-v) 通道而建立的。在这里，我们表明 CNG 通道中的离子渗透在选择性过滤器中受到严格调节。通过使用小的半胱氨酸试剂（如镉和银）扫描整个选择性过滤器，我们观察到与选择性过滤器中间的门控访问一致的状态依赖的可及性模式，可能在已知调节 KcsA 通道的结构变化以响应低浓度渗透离子的相应位置。
By opening and closing the permeation pathway (gating) in response to cGMP binding, cyclic nucleotide-gated (CNG) channels serve key roles in the transduction of visual and olfactory signals. Compiling evidence suggests that the activation gate in CNG channels is not located at the intracellular end of pore, as it has been established for voltage-activated potassium (K-v) channels. Here, we show that ion permeation in CNG channels is tightly regulated at the selectivity filter. By scanning the entire selectivity filter using small cysteine reagents, like cadmium and silver, we observed a state-dependent accessibility pattern consistent with gated access at the middle of the selectivity filter, likely at the corresponding position known to regulate structural changes in KcsA channels in response to low concentrations of permeant ions.