Mechanically-primed voltage-gated proton channels from angiosperm plants

Abstract Voltage-gated and mechanically-gated ion channels are distinct classes of membrane proteins that conduct ions across gated pores and are turned on by electrical or mechanical stimuli, respectively. Here, we describe an Hv channel (a.k.a voltage-dependent H+ channel) from the angiosperm plant A. thaliana that gates with a unique modality as it is turned on by an electrical stimulus only after exposure to a mechanical stimulus, a process that we call priming. The channel localizes in the vascular tissue and has homologs in vascular plants. We find that mechanical priming is not required for activation of non-angiosperm Hvs. Guided by AI-generated structural models of plant Hv homologs, we identify a set of residues playing a crucial role in mechanical priming. We propose that Hvs from angiosperm plants require priming because of a network of hydrophilic/charged residues that locks the channels in a silent resting conformation. Mechanical stimuli destabilize the network allowing the conduction pathway to turn on. In contrast to many other channels and receptors, Hv proteins are not thought to possess mechanisms such as inactivation or desensitization. Our findings demonstrate that angiosperm Hv channels are electrically silent until a mechanical stimulation turns on their voltage-dependent activity.