A bivalent tarantula toxin activates the capsaicin receptor, TRPV1, by targeting the outer pore domain

Cell. 2010 May 28;141(5):834-45. doi: 10.1016/j.cell.2010.03.052.


Toxins have evolved to target regions of membrane ion channels that underlie ligand binding, gating, or ion permeation, and have thus served as invaluable tools for probing channel structure and function. Here, we describe a peptide toxin from the Earth Tiger tarantula that selectively and irreversibly activates the capsaicin- and heat-sensitive channel, TRPV1. This high-avidity interaction derives from a unique tandem repeat structure of the toxin that endows it with an antibody-like bivalency. The "double-knot" toxin traps TRPV1 in the open state by interacting with residues in the presumptive pore-forming region of the channel, highlighting the importance of conformational changes in the outer pore region of TRP channels during activation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cell Line
  • Cells, Cultured
  • Electrophysiological Phenomena
  • Humans
  • Models, Molecular
  • Molecular Sequence Data
  • Neurons / metabolism
  • Oocytes / metabolism
  • Rats
  • Spider Venoms / chemistry
  • Spider Venoms / metabolism*
  • TRPV Cation Channels / chemistry
  • TRPV Cation Channels / metabolism*
  • Trigeminal Ganglion / cytology
  • Trigeminal Ganglion / metabolism
  • Xenopus Proteins / chemistry
  • Xenopus Proteins / metabolism*


  • Spider Venoms
  • TRPV Cation Channels
  • TRPV1 protein, Xenopus
  • Trpv1 protein, rat
  • Xenopus Proteins