A membrane-access mechanism of ion channel inhibition by voltage sensor toxins from spider venom.

Journal Article (Journal Article)

Venomous animals produce small protein toxins that inhibit ion channels with high affinity. In several well-studied cases the inhibitory proteins are water-soluble and bind at a channel's aqueous-exposed extracellular surface. Here we show that a voltage-sensor toxin (VSTX1) from the Chilean Rose Tarantula (Grammostola spatulata) reaches its target by partitioning into the lipid membrane. Lipid membrane partitioning serves two purposes: to localize the toxin in the membrane where the voltage sensor resides and to exploit the free energy of partitioning to achieve apparent high-affinity inhibition. VSTX1, small hydrophobic poisons and anaesthetic molecules reveal a common theme of voltage sensor inhibition through lipid membrane access. The apparent requirement for such access is consistent with the recent proposal that the sensor in voltage-dependent K+ channels is located at the membrane-protein interface.

Full Text

Duke Authors

Cited Authors

  • Lee, S-Y; MacKinnon, R

Published Date

  • July 8, 2004

Published In

Volume / Issue

  • 430 / 6996

Start / End Page

  • 232 - 235

PubMed ID

  • 15241419

Electronic International Standard Serial Number (EISSN)

  • 1476-4687

Digital Object Identifier (DOI)

  • 10.1038/nature02632


  • eng

Conference Location

  • England