Solution structure and proposed binding mechanism of a novel potassium channel toxin κ-conotoxin PVIIA

Martin J. Scanlon, David Naranjo, Linda Thomas, Paul F. Alewood, Richard J. Lewis, David J. Craik

Research output: Contribution to journalArticleResearchpeer-review

84 Citations (Scopus)


Background: κ-PVIIA is a 27-residue polypeptide isolated from the venom of Conus purpurascens and is the first member of a new class of conotoxins that block potassium channels. By comparison to other ion channels of eukaryotic cell membranes, voltage-sensitive potassium channels are relatively simple and methodology has been developed for mapping their interactions with small-peptide toxins. PVIIA, therefore, is a valuable new probe of potassium channel structure. This study of the solution structure and mode of channel binding of PVIIA forms the basis for mapping the interacting residues at the conotoxin-ion channel interface. Results: The three-dimensional structure of PVIIA resembles the triple-stranded β sheet/cystine-knot motif formed by a number of toxic and inhibitory peptides. Subtle structural differences, predominantly in loops 2 and 4, are observed between PVIIA and other conotoxins with similar structural frameworks, however. Electrophysiological binding data suggest that PVIIA blocks channel currents by binding in a voltage-sensitive manner to the external vestibule and occluding the pore. Comparison of the electrostatic surface of PVIIA with that of the well-characterised potassium channel blocker charybdotoxin suggests a likely binding orientation for PVIIA. Conclusions: Although the structure of PVIIA is considerably different to that of the αK scorpion toxins, it has a similar mechanism of channel blockade. On the basis of a comparison of the structures of PVIIA and charybdotoxin, we suggest that Lys19 of PVIIA is the residue which is responsible for physically occluding the pore of the potassium channel.

Original languageEnglish
Pages (from-to)1585-1597
Number of pages13
Issue number12
Publication statusPublished - 15 Dec 1997
Externally publishedYes


  • Charybdotoxin
  • Electrophysiology
  • NMR spectroscopy
  • Potassium-channel blockers

Cite this