Probing for the Voltage Sensor in a Mitochondrial Channel, VDAC, Using Site-Directed Mutagenesis

Abstract

The VDAC ion channel is voltage-dependent and forms a large pore across the mitochondrial outer membrane with a relatively small amount of protein. Thus, unravelling the molecular basis of voltage dependence for this channel should be an easier task than for the more complex voltage-gated channels of the plasma membrane. The ability to probe the channel for domains of the protein involved in voltage-gating, using site-directed mutations which change charge with respect to the wild type protein, has resulted in the identification of regions of the polypeptide which translocate through the transmembrane field during channel closure. The residues at which mutations alter the voltage dependence of the channel are not confined to discrete regions of the protein. Gating in VDAC seems to involve a substantial transmembrane movement of mass. There is at least one other membrane channel, colicin E1, where gating is associated with a substantial amount of mass translocated through the transmembrane field (Abrams et al., 1991).