Biological processes as diverse as neuronal signaling, muscle contraction, the immune response, and the heart beat depend on the proper function of proteins containing voltage-sensing domains (VSDs). In recent years, our view on these domains has changed dramatically. Once regarded as simple modulators of pore domains in voltage-gated sodium, potassium, and calcium channels, they are now recognized as structural units that perform different tasks in different proteins, as they control the activity of enzymatic domains in voltage-sensitive phosphatases, act as gated pores in voltage-gated proton channels, and sense chemical signals in thermosensitive TRP channels. VSD malfunction, or misregulation, is the cause of neurological disorders, cardiac arrhythmias, and cancer. In this talk I will focus on the structural organization and function of the voltage-gated proton channel Hv1 as a model for ion permeable VSDs.

Voltage-sensing domain of voltage-gated proton channel Hv1 shares mechanism of block with pore domains. Neuron 77(2) 274-286 (2013)
The opening of the two pores of the Hv1 voltage-gated proton channel is tuned by cooperativity. Nat. Struct. Mol. Biol. 17(1), 44-50 (2010)
The voltage-gated proton channel Hv1 has two pores, each controlled by one voltage sensor. Neuron 58(4), 546-556 (2008)
The twisted ion-permeation pathway of a resting voltage-sensing domain. Nature 445(7127), 546-549 (2007)