Crystallographic study of the tetrabutylammonium block to the KcsA K+ channel.
Crystallographic study of the tetrabutylammonium block to the KcsA K+ channel.
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KcsA K 通道四丁基铵阻断的晶体学研究。
DOI：
10.1016/j.jmb.2006.11.081
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发表时间：
2007
影响因子：
5.6
通讯作者：
Zhou,Yufeng
中科院分区：
文献类型：
--
作者：
Yohannan,Sarah;Hu,Yue;Zhou,Yufeng
K+通道通过选择性地将K+离子输送到细胞膜的孔中，在调节多种细胞的膜兴奋性方面起着至关重要的作用。许多不同的分子可以堵塞毛孔，调节K+电流。季铵(QA)离子是一类孔道阻滞剂，几十年来一直被生物物理学家用来探测孔道，从而对K+通道的结构与功能关系有了重要的认识。然而，到目前为止，QA阻止机制的许多关键方面仍然不清楚，理解这些问题需要高分辨率的结构信息。在这里，我们讨论了细胞内QA阻断是否导致K+通道选择性过滤器的构象变化的问题。我们解决了在不同离子条件下四丁基铵(TBA)和四丁基锑(TBSb)络合物中KCsA钾离子通道的结构。我们的结果表明，在高浓度的离子作用下，TBA或TBSB的结合不会引起KCSA结构的显著变化。我们确实观察到了低K+浓度下滤膜的预期构象变化，但这种变化似乎与TBA或TBSB的阻断无关。
K+channels play essential roles in regulating membrane excitability of many diverse cell types by selectively conducting K+ions through their pores. Many diverse molecules can plug the pore and modulate the K+current. Quaternary ammonium (QA) ions are a class of pore blockers that have been used for decades by biophysicists to probe the pore, leading to important insights into the structure–function relation of K+channels. However, many key aspects of the QA-blocking mechanisms remain unclear to date, and understanding these questions requires high resolution structural information. Here, we address the question of whether intracellular QA blockade causes conformational changes of the K+channel selectivity filter. We have solved the structures of the KcsA K+channel in complex with tetrabutylammonium (TBA) and tetrabutylantimony (TBSb) under various ionic conditions. Our results demonstrate that binding of TBA or TBSb causes no significant change in the KcsA structure at high concentrations of permeant ions. We did observe the expected conformational change of the filter at low concentration of K+, but this change appears to be independent of TBA or TBSb blockade.