Molecular mechanism of Zn 2+ inhibition of a voltage-gated proton channel

Significance Zn 2+ inhibition of voltage-gated proton (Hv1) channels has important physiological roles, such as quiescence of sperm in the male reproductive system. Here, we show that Zn 2+ binds to different states of Hv1, and we propose a possible mechanism for Zn 2+ inhibition of Hv1. Several residues are found to be involved in Zn 2+ binding, and we provide detailed information about how these residues contribute to the functional effect of Zn 2+ binding. This study provides valuable information for future drug development for Hv1 channels.