The Translocation Domain of Botulinum Neurotoxin A Moderates the Propensity of the Catalytic Domain to Interact with Membranes at Acidic pH - Institut Pasteur Accéder directement au contenu
Article Dans Une Revue PLoS ONE Année : 2016

The Translocation Domain of Botulinum Neurotoxin A Moderates the Propensity of the Catalytic Domain to Interact with Membranes at Acidic pH

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Botulinum neurotoxin A (BoNT/A) is composed of three domains: a catalytic domain (LC), a translocation domain (H N) and a receptor-binding domain (H C). Like most bacterial toxins BoNT/A is an amphitropic protein, produced in a soluble form that is able to interact, penetrate and/or cross a membrane to achieve its toxic function. During intoxication BoNT/A is internalized by the cell by receptor-mediated endocytosis. Then, LC crosses the membrane of the endocytic compartment and reaches the cytosol. This translocation is initiated by the low pH found in this compartment. It has been suggested that LC passes in an unfolded state through a transmembrane passage formed by H N. We report here that acidification induces no major conformational change in either secondary or tertiary structures of LC and H N of BoNT/A in solution. GdnHCl-induced denaturation experiments showed that the stability of LC and H N increases as pH drops, and that H N further stabilizes LC. Unexpectedly we found that LC has a high propensity to interact with and permeabilize anionic lipid bilay-ers upon acidification without the help of H N. This property is downplayed when LC is linked to H N. H N thus acts as a chaperone for LC by enhancing its stability but also as a moderator of the membrane interaction of LC.
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pasteur-01378747 , version 1 (10-10-2016)

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Anne Araye, Amélie Goudet, Julien Barbier, Sylvain Pichard, Bruno Baron, et al.. The Translocation Domain of Botulinum Neurotoxin A Moderates the Propensity of the Catalytic Domain to Interact with Membranes at Acidic pH. PLoS ONE, 2016, 11 (4), pp.e0153401. ⟨10.1371/journal.pone.0153401⟩. ⟨pasteur-01378747⟩
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