Binding of a gating modifier toxin induces intersubunit cooperativity early in the Shaker K channel's activation pathway.
Binding of a gating modifier toxin induces intersubunit cooperativity early in the Shaker K channel's activation pathway.
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DOI：
10.1085/jgp.200609492
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发表时间：
2006-07
期刊：
影响因子：
--
通讯作者：
Aldrich RW
中科院分区：
文献类型：
--
作者：
Sack JT;Aldrich RW
电压门控振荡器钾通道的钾电流以S形上升激活。通道开放动力学中的S型程度证实了同源四聚体振荡器通道的每个亚基在通道开放之前经历了不止一次的构象变化。我们研究了两种外用门控修饰剂的效果，这两种修饰剂降低了通道开口的S型。腹足类粘液中的一种毒素，6-溴-2-巯基色胺(BrMT)和二价锌都被发现在Shaker激活途径的早期减缓相同的构象变化。Sigmoidity测量表明，锌独立地减缓了每个通道亚基的构象变化。对BrMT的激活分析表明，在这些相同的早期步骤中，亚基之间存在协同作用。与激动素或四乙基铵缺乏竞争表明BrMT以变构合作的方式与外部孔区外的通道亚基结合。包括负合作BrMT结合的模拟说明了它在激活过程中诱导门控协同作用的能力。我们得出结论，K通道亚基之间的协作性可以被实验条件极大地改变。
Potassium currents from voltage-gated Shaker K channels activate with a sigmoid rise. The degree of sigmoidicity in channel opening kinetics confirms that each subunit of the homotetrameric Shaker channel undergoes more than one conformational change before the channel opens. We have examined effects of two externally applied gating modifiers that reduce the sigmoidicity of channel opening. A toxin from gastropod mucus, 6-bromo-2-mercaptotryptamine (BrMT), and divalent zinc are both found to slow the same conformational changes early in Shaker's activation pathway. Sigmoidicity measurements suggest that zinc slows a conformational change independently in each channel subunit. Analysis of activation in BrMT reveals cooperativity among subunits during these same early steps. A lack of competition with either agitoxin or tetraethylammonium indicates that BrMT binds channel subunits outside of the external pore region in an allosterically cooperative fashion. Simulations including negatively cooperative BrMT binding account for its ability to induce gating cooperativity during activation. We conclude that cooperativity among K channel subunits can be greatly altered by experimental conditions.
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影响因子：
56.9
作者：
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