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Characterization of a Membrane-active Peptide from the Bordetella pertussis CyaA Toxin

Abstract : Bordetella pertussis, the pathogenic bacteria responsible for whooping cough, secretes several virulence factors, among which is the adenylate cyclase toxin (CyaA) that plays a crucial role in the early stages of human respiratory tract colonization. CyaA invades target cells by translocating its catalytic domain directly across the plasma membrane and overproduces cAMP, leading to cell death. The molecular process leading to the translocation of the catalytic domain remains largely unknown. We have previously shown that the catalytic domain per se, AC384, encompassing residues 1-384 of CyaA, did not interact with lipid bilayer, whereas a longer polypeptide, AC489, spanning residues 1-489, binds to membranes and permeabilizes vesicles. Moreover, deletion of residues 375-485 within CyaA abrogated the translocation of the catalytic domain into target cells. Here, we further identified within this region a peptidic segment that exhibits membrane interaction properties. A synthetic peptide, P454, corresponding to this sequence (residues 454-485 of CyaA) was characterized by various biophysical approaches. We found that P454 (i) binds to membranes containing anionic lipids, (ii) adopts an α-helical structure oriented in plane with respect to the lipid bilayer, and (iii) permeabilizes vesicles. We propose that the region encompassing the helix 454-485 of CyaA may insert into target cell membrane and induce a local destabilization of the lipid bilayer, thus favoring the translocation of the catalytic domain across the plasma membrane.
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https://hal.archives-ouvertes.fr/hal-00937043
Contributor : Francesco Di Renzo <>
Submitted on : Monday, January 27, 2014 - 4:53:27 PM
Last modification on : Tuesday, February 9, 2021 - 11:24:38 AM

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Orso Subrini, Ana-Cristina Sotomayor-Pérez, Audrey Hessel, Johanna Spiaczka-Karst, Edithe Selwa, et al.. Characterization of a Membrane-active Peptide from the Bordetella pertussis CyaA Toxin. Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 2013, 288 (45), pp.32585-32598. ⟨10.1074/jbc.M113.508838⟩. ⟨hal-00937043⟩

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