New tricks of an old pattern: structural versatility of scorpion toxins with common cysteine spacing

J Biol Chem. 2012 Apr 6;287(15):12321-30. doi: 10.1074/jbc.M111.329607. Epub 2012 Jan 10.


Scorpion venoms are a rich source of K(+) channel-blocking peptides. For the most part, they are structurally related small disulfide-rich proteins containing a conserved pattern of six cysteines that is assumed to dictate their common three-dimensional folding. In the conventional pattern, two disulfide bridges connect an α-helical segment to the C-terminal strand of a double- or triple-stranded β-sheet, conforming a cystine-stabilized α/β scaffold (CSα/β). Here we show that two K(+) channel-blocking peptides from Tityus scorpions conserve the cysteine spacing of common scorpion venom peptides but display an unconventional disulfide pattern, accompanied by a complete rearrangement of the secondary structure topology into a CS helix-loop-helix fold. Sequence and structural comparisons of the peptides adopting this novel fold suggest that it would be a new elaboration of the widespread CSα/β scaffold, thus revealing an unexpected structural versatility of these small disulfide-rich proteins. Acknowledgment of such versatility is important to understand how venom structural complexity emerged on a limited number of molecular scaffolds.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs
  • Amino Acid Sequence
  • Animals
  • Chromatography, High Pressure Liquid
  • Chromatography, Reverse-Phase
  • Cysteine / chemistry*
  • Membrane Potentials / drug effects
  • Molecular Sequence Data
  • Nuclear Magnetic Resonance, Biomolecular
  • Protein Structure, Tertiary
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / isolation & purification
  • Recombinant Fusion Proteins / pharmacology
  • Scorpion Venoms / chemistry*
  • Scorpion Venoms / isolation & purification
  • Scorpion Venoms / pharmacology
  • Scorpions*
  • Sequence Analysis, Protein
  • Structural Homology, Protein
  • Surface Properties
  • Xenopus


  • Recombinant Fusion Proteins
  • Scorpion Venoms
  • Cysteine

Associated data

  • PDB/2LI3
  • PDB/2LKA