Interaction of a toxin from the scorpion Tityus serrulatus with a cloned K+ channel from squid (sqKv1A)

Biochemistry. 2001 May 22;40(20):5942-53. doi: 10.1021/bi010173g.


A toxin from the scorpion Tityus serrulatus (TsTX-Kalpha) blocks native squid K(+) channels and their cloned counterpart, sqKv1A, at pH 8 ((native)K(d) approximately 20 nM; (sqKv1A)K(d) approximately 10 nM). In both cases, decreasing the pH below 7.0 significantly diminishes the TsTX-Kalpha effect (pK = 6.6). In the cloned squid channel, the pH dependence of the block is abolished by a single point mutation (H351G), and no change in toxin affinity was observed at higher pH values (pH > or =8.0). To further investigate the TsTX-Kalpha-sqKv1A interaction, the three-dimensional structure of TsTX-Kalpha was determined in solution by NMR spectroscopy, and a model of the TsTX-Kalpha-sqKv1A complex was generated. As found for other alpha-K toxins such as charybdotoxin (CTX), site-directed mutagenesis at toxin residue K27 (K27A, K27R, and K27E) significantly reduced the toxin's affinity for sqKv1A channels. This is consistent with the TsTX-Kalpha-sqKv1A model reported here, which has K27 of the toxin inserted into the ion conduction pathway of the K(+) channel. This toxin-channel model also illustrates a possible mechanism for the pH-dependent block whereby lysine residues from TsTX-Kalpha (K6 and K23) are repelled by protonated H351 on sqKv1A at low pH.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cloning, Molecular
  • Decapodiformes
  • Delayed Rectifier Potassium Channels
  • Ganglia, Invertebrate / chemistry
  • Ganglia, Invertebrate / drug effects
  • Ganglia, Invertebrate / physiology
  • Models, Molecular
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Neurotoxins / chemistry*
  • Neurotoxins / genetics
  • Neurotoxins / metabolism
  • Neurotoxins / pharmacology
  • Nuclear Magnetic Resonance, Biomolecular
  • Oocytes
  • Potassium Channel Blockers
  • Potassium Channels / chemistry*
  • Potassium Channels / genetics
  • Potassium Channels, Voltage-Gated*
  • Protein Structure, Secondary
  • Recombinant Proteins / antagonists & inhibitors
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / metabolism
  • Scorpion Venoms / chemistry*
  • Scorpion Venoms / genetics
  • Scorpion Venoms / pharmacology
  • Sequence Homology, Amino Acid
  • Xenopus laevis


  • Delayed Rectifier Potassium Channels
  • Neurotoxins
  • Potassium Channel Blockers
  • Potassium Channels
  • Potassium Channels, Voltage-Gated
  • Recombinant Proteins
  • Scorpion Venoms
  • tityustoxin