Evaluation of the free energy of proton transport through the Hv1 channel reveals that D112 allows protons to bypass the electrostatic barrier in the open conformation.
The action of the Hv1 proton channel is controlled by the protein electrostatic potential at rate-limiting barriers rather than a Grotthuss mechanism.
The nature of the action of voltage-activated proton transport proteins is a conundrum of great current interest. Here we approach this issue by exploring the action of Hv1, a voltage-gated proton channel found in different cells in humans and other organisms. Our study focuses on evaluating the free energy of transporting a proton through the channel, as well as the effect of the proton transfer through D112, in both the closed and open channel conformations. It is found that D112 allows a transported proton to bypass the electrostatic barrier of the open channel, while not being able to help in passing the barrier in the closed form. This reflects the change in position of the gating arginine residues relative to D112, upon voltage activation. Significantly, the effect of D112 accounts for the observed trend in selectivity by overcoming the electrostatic barrier at its highest point. Thus, the calculations provide a structure/function correlation for the Hv1 system. The present work also clarifies that the action of Hv1 is not controlled by a Grotthuss mechanism but, as is always the case, by the protein electrostatic potential at the rate-limiting barriers.
Lee et al. (Tue,) conducted a other in Voltage-gated proton channel Hv1 function. Evaluation of the free energy of proton transport through the Hv1 channel reveals that D112 allows protons to bypass the electrostatic barrier in the open conformation.