The voltage-gated proton channel Hv1 is a member of the voltage-gated ion channel superfamily, which stands out in design: It is a dimer of two voltage-sensing domains (VSDs), each containing a pore pathway, a voltage sensor (S4), and a gate (S1) and forming its own ion channel. Opening of the two channels in the dimer is cooperative. Part of the cooperativity is due to association between coiled-coil domains that extend intracellularly from the S4s. Interactions between the transmembrane portions of the subunits may also contribute, but the nature of transmembrane packing is unclear. Using functional analysis of a mutagenesis scan, biochemistry, and modeling, we find that the subunits form a dimer interface along the entire length of S1, and also have intersubunit contacts between S1 and S4. These interactions exert a strong effect on gating, in particular on the stability of the open state. Our results suggest that gating in Hv1 is tuned by extensive VSD–VSD interactions between the gates and voltage sensors of the dimeric channel.

电压门控质子通道 Hv1 是电压门控离子通道超家族的一员，在设计上脱颖而出：它是两个电压传感域 (VSD) 的二聚体，每个域包含一个孔道、一个电压传感器 (S4) ）和门（S1）并形成其自己的离子通道。二聚体中两个通道的打开是协同的。部分协同作用是由于从 S4 延伸到细胞内的卷曲螺旋结构域之间的关联。亚基跨膜部分之间的相互作用也可能有所贡献，但跨膜堆积的性质尚不清楚。通过诱变扫描、生物化学和建模的功能分析，我们发现亚基沿着 S1 的整个长度形成二聚体界面，并且 S1 和 S4 之间也有亚基间接触。这些相互作用对门控产生强烈影响，特别是对开放状态的稳定性。我们的结果表明，Hv1 中的门控是通过二聚体通道的门和电压传感器之间广泛的 VSD-VSD 相互作用来调节的。