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Approche biophysique de l'étude de l'insertion du domaine de translocation de la toxine botulique dans les membranes

Abstract : Botulinum neurotoxins (BoNTs), the most potent known toxins, are responsible for botulism. They inhibit acetylcholine release at the neuromuscular junction, inducing a flaccid paralysis. Upon intoxication, BoNT binds to its receptor at the plasma membrane of neurons and is then internalized by endocytosis. Inside acidic compartments, the interaction of its translocation domain with the membrane drives the translocation of the catalytic domain into the cytosol. The translocation domain of BoNT/A (Tm) was expressed and produced using a synthetic gene. Its insertion and activity have been shown to be pH dependent and to occur below pH 5.5. No structural change could be detected by spectroscopy. However, the formation of a quaternary structure is still possible. The sensitivity of Tm activity to membrane curvature has been observed. This could be an additional control to its function.

Apomyoglobin belongs to the globin fold family which counts several bacterial toxin domains as members. Its interaction with membranes shares some characteristics with that of the translocation domain of diphtheria toxin. It is a pH-dependent two-step process (binding and insertion) which requires the accumulation of a partially unfolded state. The protein parts involved in each step have been identified using Hydrogen/Deuterium exchanges analyzed by mass spectrometry. An amphipathic helix allows the membrane binding, and a hydrophobic helix is involved in the insertion step. The last helix becomes available upon formation of the partially folded state.
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https://tel.archives-ouvertes.fr/tel-00264440
Contributor : Caroline Montagner <>
Submitted on : Monday, March 17, 2008 - 11:38:57 AM
Last modification on : Wednesday, November 4, 2020 - 2:01:16 PM
Long-term archiving on: : Thursday, May 20, 2010 - 9:11:51 PM

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  • HAL Id : tel-00264440, version 1

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Caroline Montagner. Approche biophysique de l'étude de l'insertion du domaine de translocation de la toxine botulique dans les membranes. Biochimie [q-bio.BM]. Université Joseph-Fourier - Grenoble I, 2007. Français. ⟨tel-00264440⟩

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