The cytoplasmic coiled-coil mediates cooperative gating temperature sensitivity in the voltage-gated H+ channel Hv1
The cytoplasmic coiled-coil mediates cooperative gating temperature sensitivity in the voltage-gated H+ channel Hv1
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DOI：
10.1038/ncomms1823
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发表时间：
2012-05-01
影响因子：
16.6
通讯作者：
Okamura, Yasushi
中科院分区：
文献类型：
--
作者：
Fujiwara, Yuichiro;Kurokawa, Tatsuki;Okamura, Yasushi
Hv 1/VSOP是一种二聚体电压门控H+通道，其中一个亚基的门控与二聚体中另一个亚基的门控偶联。然而，二聚体形成和亚基间偶联的分子基础仍然未知。在这里，我们表明，羧基末端下游的S4电压传感器螺旋扭曲的二聚体卷曲螺旋结构，介导的合作门控。我们还表明，通过Hv 1/VSOP的H+电流的温度依赖性激活受卷曲螺旋结构域的热稳定性调节，并且这种调节通过S4和卷曲螺旋之间的连接子的突变而改变。二聚体内的合作门控也取决于连接体结构，圆二色光谱分析表明其为α-螺旋。我们的研究结果表明，细胞质卷曲螺旋链与S4形成连续的α-螺旋，并介导合作门控以调节Hv 1/VSOP操作的温度范围。
Hv1/VSOP is a dimeric voltage-gated H+ channel in which the gating of one subunit is reportedly coupled to that of the other subunit within the dimer. The molecular basis for dimer formation and intersubunit coupling, however, remains unknown. Here we show that the carboxy terminus ends downstream of the S4 voltage-sensor helix twist in a dimer coiled-coil architecture, which mediates cooperative gating. We also show that the temperature-dependent activation of H+ current through Hv1/VSOP is regulated by thermostability of the coiled-coil domain, and that this regulation is altered by mutation of the linker between S4 and the coiled-coil. Cooperative gating within the dimer is also dependent on the linker structure, which circular dichroism spectrum analysis suggests is alpha-helical. Our results indicate that the cytoplasmic coiled-coil strands form continuous alpha-helices with S4 and mediate cooperative gating to adjust the range of temperatures over which Hv1/VSOP operates.