Referenced in: none

Automatically associated channels: Kv1.2 , Kv1.3

Title: Disulfide bridge reorganization induced by proline mutations in maurotoxin.

Authors: E Carlier, Z Fajloun, P Mansuelle, M Fathallah, A Mosbah, R Oughideni, G Sandoz, E Di Luccio, S Geib, I Regaya, J Brocard, H Rochat, H Darbon, C Devaux, J M Sabatier, M De Waard

Journal, date & volume: FEBS Lett., 2001 Feb 2 , 489, 202-7

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/11165250

Abstract
Maurotoxin (MTX) is a 34-residue toxin that has been isolated from the venom of the chactidae scorpion Scorpio maurus palmatus, and characterized. Together with Pi1 and HsTx1, MTX belongs to a family of short-chain four-disulfide-bridged scorpion toxins acting on potassium channels. However, contrary to other members of this family, MTX exhibits an uncommon disulfide bridge organization of the type C1-C5, C2-C6, C3-C4 and C7-C8, versus C1-C5, C2-C6, C3-C7 and C4-C8 for both Pi1 and HsTx1. Here, we report that the substitution of MTX proline residues located at positions 12 and/or 20, adjacent to C3 (Cys(13)) and C4 (Cys(19)), results in conventional Pi1- and HsTx1-like arrangement of the half-cystine pairings. In this case, this novel disulfide bridge arrangement is without obvious incidence on the overall three-dimensional structure of the toxin. Pharmacological assays of this structural analog, [A(12),A(20)]MTX, reveal that the blocking activities on Shaker B and rat Kv1.2 channels remain potent whereas the peptide becomes inactive on rat Kv1.3. These data indicate, for the first time, that discrete point mutations in MTX can result in a marked reorganization of the half-cystine pairings, accompanied with a novel pharmacological profile for the analog.