A distinct three-helix centipede toxin SSD609 inhibits I(ks) channels by interacting with the KCNE1 auxiliary subunit

Sci Rep. 2015 Aug 26;5:13399. doi: 10.1038/srep13399.


KCNE1 is a single-span transmembrane auxiliary protein that modulates the voltage-gated potassium channel KCNQ1. The KCNQ1/KCNE1 complex in cardiomyocytes exhibited slow activated potassium (I(ks)) currents. Recently, a novel 47-residue polypeptide toxin SSD609 was purified from Scolopendra subspinipes dehaani venom and showed I(ks) current inhibition. Here, chemically synthesized SSD609 was shown to exert I(ks) inhibition in extracted guinea pig cardiomyocytes and KCNQ1/KCNE1 current attenuation in CHO cells. The K(+) current attenuation of SSD609 showed decent selectivity among different auxiliary subunits. Solution nuclear magnetic resonance analysis of SSD609 revealed a distinctive three-helix conformation that was stabilized by a new disulfide bonding pattern as well as segregated surface charge distribution. Structure-activity studies demonstrated that negatively charged Glu19 in the amphipathic extracellular helix of KCNE1 was the key residue that interacted with SSD609. The distinctive three-helix centipede toxin SSD609 is known to be the first polypeptide toxin acting on channel auxiliary subunit KCNE1, which suggests a new type of pharmacological regulation for ion channels in cardiomyocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Arthropod Venoms / administration & dosage*
  • Arthropod Venoms / chemistry*
  • Binding Sites
  • Computer Simulation
  • Dose-Response Relationship, Drug
  • Ion Channel Gating / drug effects
  • Ion Channel Gating / physiology
  • Models, Biological
  • Models, Chemical*
  • Models, Molecular*
  • Molecular Sequence Data
  • Myocytes, Cardiac / drug effects
  • Myocytes, Cardiac / metabolism*
  • Potassium Channel Blockers / administration & dosage
  • Potassium Channel Blockers / chemistry
  • Potassium Channels, Voltage-Gated / drug effects
  • Potassium Channels, Voltage-Gated / metabolism*
  • Protein Binding
  • Protein Conformation
  • Protein Structure, Tertiary
  • Protein Subunits
  • Structure-Activity Relationship


  • Arthropod Venoms
  • KCNE1 protein, human
  • Potassium Channel Blockers
  • Potassium Channels, Voltage-Gated
  • Protein Subunits