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

Structure
M J ScanlonDavid J Craik

Abstract

kappa-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. The three-dimensional structure of PVIIA resembles the triple-stranded beta 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 like...Continue Reading

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Citations

Oct 24, 2003·Journal of Structural Biology·Christopher E JonesCharles T Dameron
Aug 11, 2000·Toxicon : Official Journal of the International Society on Toxinology·D J CraikC Waine
Aug 2, 2003·Toxicon : Official Journal of the International Society on Toxinology·Silke KaufersteinDietrich Mebs
Oct 16, 2003·Toxicon : Official Journal of the International Society on Toxinology·Kimberly Laskie OstrowPhilip A Gottlieb
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Jun 13, 2015·Expert Opinion on Therapeutic Patents·Thomas Durek, David J Craik
Jun 26, 2015·Toxins·Quentin Kaas, David J Craik
Mar 3, 2011·Current Opinion in Chemical Biology·Norelle L Daly, David J Craik
May 12, 2015·Advanced Drug Delivery Reviews·Changyou ZhanWeiyue Lu
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Apr 20, 2016·Biotechnology and Bioengineering·Soohyun KwonDavid J Craik
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Jul 26, 2007·ACS Chemical Biology·David J Craik, David J Adams

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