Small molecule discovery for modulation of Otopetrin proton channels

Proton conductance across the plasma membrane is involved in many biological roles, ranging from sour taste reception to regulation of intracellular and extracellular pH. Recently, a eukaryotic family of membrane-bound proteins, named Otopetrins, were characterized as proton channels. Otopetrins elicit inward conducting proton currents in response to low extracellular pH levels. Cryo-electron microscopy structures of Otopetrins revealed that they bear no structural similarity to other proton channels, like the voltage-gated proton channel Hv1 or the influenza proton channel M2, marking them a new architecture for proton channels.