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Bases structurales de la specificite de reconnaissance entre les toxines animales et les canaux ioniques

Abstract : Ionic channels are of crucial importance as they are involved in numerous biological processes. In the aim of finding an efficient treatment against diseases, those are produced by a functional alteration of such channels, the understanding of functional mechanisms of these channels is the main goal to reach. Animal toxins acting against ionic channels are valuable tools for probing channel's pharmacological and structural properties. This manuscript present the K+, Na+ and Ca2+ channels and their natural blockers : animal toxins. These toxins are organized around two main structural motifs : the CsΑΒ motif (Cystine stabilized ΑΒ motif), mainly described for scorpion toxins acting against K+ and Na+ channels, and the ICK motif (Inhibitor Cystine Knot) encountered in many conotoxins and spider toxins that are active on Ca2+, K+ or Na+ channels. The work presented in this manuscript is underlined by the goal to improve the knowledge and understandings of the molecular interaction between a toxin and an ionic channel. The results are organized around the NMR solution structure determination of such toxins. Concerning the CsΑΒ motif, the conception of toxin chimaeras shows that the specificity and/or the selectivity of the toxin toward a type of K+ channel can be modified. Considering the toxins organized around the ICK structural motif, our results concerning those acting against K+ channels have to be confirmed with some more experiments: the structure indicates these toxins might be pore channel blockers whereas biological assay purposes these toxins acting as gating modifiers. Concerning the toxins that are active on Ca2+ channels, the specificity against the different channel's subtypes and the influence of the anisotropy of electrostatic charges repartition on the interaction between the toxin and the channel are discussed.
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https://tel.archives-ouvertes.fr/tel-00010404
Contributor : Cedric Bernard <>
Submitted on : Wednesday, October 5, 2005 - 11:12:13 AM
Last modification on : Thursday, December 3, 2020 - 5:12:03 PM
Long-term archiving on: : Friday, April 2, 2010 - 10:15:14 PM

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Cedric Bernard. Bases structurales de la specificite de reconnaissance entre les toxines animales et les canaux ioniques. Biochimie [q-bio.BM]. Université de la Méditerranée - Aix-Marseille II, 2002. Français. ⟨tel-00010404⟩

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