Jun 15, 1993

Mapping of residues forming the voltage sensor of the voltage-dependent anion-selective channel

Proceedings of the National Academy of Sciences of the United States of America
L ThomasM Forte

Abstract

Voltage-gated ion-channel proteins contain "voltage-sensing" domains that drive the conformational transitions between open and closed states in response to changes in transmembrane voltage. We have used site-directed mutagenesis to identify residues affecting the voltage sensitivity of a mitochondrial channel, the voltage-dependent anion-selective channel (VDAC). Although charge changes at many sites had no effect, at other sites substitutions that increased positive charge also increased the steepness of voltage dependence and substitutions that decreased positive charge decreased voltage dependence by an appropriate amount. In contrast to the plasma membrane K+ and Na+ channels, these residues are distributed over large parts of the VDAC protein. These results have been used to define the conformational transitions that accompany voltage gating of an ion channel. This gating mechanism requires the movement of large portions of the VDAC protein through the membrane.

  • References59
  • Citations76

Citations

Mentioned in this Paper

Proteins, Recombinant DNA
Mutagenesis, Site-Directed
Integral to Membrane
Electric Conductivity
Ion Channel
Dextran Sulfate Sodium
Mitochondria
Voltage-Dependent Anion Channels
Pore Proteins
Cell Surface Proteins

About this Paper

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