MAPPING OF RESIDUES FORMING THE VOLTAGE SENSOR OF THE VOLTAGE-DEPENDENT ANION-SELECTIVE CHANNEL

Voltage-gated ion-channel proteins contain ''voltage-sensing'' domains that drive the conformational transitions between open and closed sta tes in response to changes in transmembrane voltage. We have used site -directed mutagenesis to identify residues affecting the voltage sensi tivity of a mitochondrial channel, the voltage-dependent anion-selecti ve channel (VDAC). Although charge changes at many sites had no effect , at other sites substitutions that increased positive charge also inc reased the steepness of voltage dependance and substitutions that decr eased positive charge decreased voltage dependance by an appropriate a mount. In contrast to the plasma membrane K+ and Na+ channels, these r esidues are distributed over large parts of the VDAC protein. These re sults have been used to define the conformational transitions that acc ompany voltage gating of an ion channel. This gating mechanism require s the movement of large portions of the VDAC protein through the membr ane.