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 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.
Thomas
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L
Department of Zoology, University of Maryland, College Park 20742.
Blachly-Dyson
E
E
Colombini
M
M
Forte
M
M
D000595:Amino Acid Sequence; D003001:Cloning, Molecular; D016264:Dextran Sulfate / Q000494:pharmacology; D004553:Electric Conductivity; D007473:Ion Channels / Q000502:physiology*; D008051:Lipid Bilayers; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D008961:Models, Structural; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D018272:Porins; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics; D050994:Voltage-Dependent Anion Channels
D007473:Ion Channels; D008051:Lipid Bilayers; D008565:Membrane Proteins; D018272:Porins; D011994:Recombinant Proteins; D050994:Voltage-Dependent Anion Channels; D016264:Dextran Sulfate