Voltage-activated ion channels contain S1-S4 domains that sense membrane voltage and control opening of ion-selective pores, a mechanism that is crucial for electrical signaling. Related S1-S4 domains have been identified in voltage-sensitive phosphatases and voltage-activated proton channels, both of which lack associated pore domains. hTMEM266 is a protein of unknown function that is predicted to contain an S1-S4 domain, along with partially structured cytoplasmic termini. Here we show that hTMEM266 forms oligomers, undergoes both rapid (µs) and slow (ms) structural rearrangements in response to changes in voltage, and contains a Zn2+ binding site that can regulate the slow conformational transition. Our results demonstrate that the S1-S4 domain in hTMEM266 is a functional voltage sensor, motivating future studies to identify cellular processes that may be regulated by the protein. The ability of hTMEM266 to respond to voltage on the µs timescale may be advantageous for designing new genetically encoded voltage indicators.

Background The COVID-19 pandemic has impacted the U.S. economy and workforce, with marked effects on small businesses. Studies have evaluated workers’ views of financial confidence and advancement, but there has been limited focus on the dental industry. Methods To extend investigations to dentistry, published scales and pretested questions were used to determine workforce confidence and workflow changes among dentists. Data were evaluated using descriptive and bivariate statistics. In the wake of the pandemic, surveys were distributed to the American Dental Association (ADA) and American Association of Orthodontics (AAO) membership (N=656). Results Dentists’ top concern is increased cost of providing treatment (57.4% [Confidence Interval (CI): 53.5, 61.3]), associated with widely adopted workflow changes including reduced patient volumes (66.0% [CI: 62.4, 69.6]) and increased safety protocols and equipment (health screening, 75.5% [CI: 72.2, 78.8]), KN/N95 masks, 76.7% [CI: 73.5, 80.0]). However, the majority of respondents do not expect their personal or practice finances to be negatively affected after the pandemic, as only 18.5% ([CI: 15.4, 21.7]) predict their practice’s gross revenue to decrease. Conclusions Dentists are optimistic in the wake of vaccinations and lifting restrictions. Most expect their finances and practice performance to remain the same or grow in the short-term and expect long-term improvements post-pandemic. Practical Implications Results suggest that despite shutdowns and workflow changes, dentists have financially rebounded and anticipate future growth.

The voltage-gated proton channel Hv1 plays a key role in the regulation of ROS production by NOX enzymes in phagocytic cells. Excessive channel activity enhances proliferation and invasiveness in cancer cells, and worsens brain damage after ischemic stroke. The Hv1 channel is composed of two subunits, each containing a proton-permeable voltage-sensing domain (VSD) and lacking the pore domain typical of other voltage-gated ion channels. We have previously shown that the compound 2-guanidinobenzimidazole (2GBI) inhibits the Hv1

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