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Toxins 2017, 9(11), 369; doi:10.3390/toxins9110369

Membrane-Active Properties of an Amphitropic Peptide from the CyaA Toxin Translocation Region

1
Département de Biologie Structurale et Chimie, Institut Pasteur, Unité de Biochimie des Interactions Macromoléculaires, CNRS UMR 3528, 28 Rue du Dr Roux, 75724 Paris, CEDEX 15, France
2
Université Paris Diderot Paris VII, 75013 Paris, France
3
Institut de Biologie Structurale, 71 Avenue des Martyrs, 38044 Grenoble, CEDEX 9, France
4
Bioaster Technology Research Institute, 69007 Lyon, France
*
Authors to whom correspondence should be addressed.
Academic Editor: Holger Barth
Received: 18 October 2017 / Revised: 9 November 2017 / Accepted: 10 November 2017 / Published: 14 November 2017
(This article belongs to the Special Issue Adenylate Cyclase (CyaA) Toxin)
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Abstract

The adenylate cyclase toxin CyaA is involved in the early stages of infection by Bordetella pertussis, the causative agent of whooping cough. CyaA intoxicates target cells by a direct translocation of its catalytic domain (AC) across the plasma membrane and produces supraphysiological levels of cAMP, leading to cell death. The molecular process of AC translocation remains largely unknown, however. We have previously shown that deletion of residues 375–485 of CyaA selectively abrogates AC translocation into eukaryotic cells. We further identified within this “translocation region” (TR), P454 (residues 454–484), a peptide that exhibits membrane-active properties, i.e., is able to bind and permeabilize lipid vesicles. Here, we analyze various sequences from CyaA predicted to be amphipatic and show that although several of these peptides can bind membranes and adopt a helical conformation, only the P454 peptide is able to permeabilize membranes. We further characterize the contributions of the two arginine residues of P454 to membrane partitioning and permeabilization by analyzing the peptide variants in which these residues are substituted by different amino acids (e.g., A, K, Q, and E). Our data shows that both arginine residues significantly contribute, although diversely, to the membrane-active properties of P454, i.e., interactions with both neutral and anionic lipids, helix formation in membranes, and disruption of lipid bilayer integrity. These results are discussed in the context of the translocation process of the full-length CyaA toxin. View Full-Text
Keywords: membrane-active peptide; adenylate cyclase; CyaA toxin; repeat in toxin; membrane partitioning-folding coupling; membrane disruption; arginine side chain membrane-active peptide; adenylate cyclase; CyaA toxin; repeat in toxin; membrane partitioning-folding coupling; membrane disruption; arginine side chain
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Voegele, A.; Subrini, O.; Sapay, N.; Ladant, D.; Chenal, A. Membrane-Active Properties of an Amphitropic Peptide from the CyaA Toxin Translocation Region. Toxins 2017, 9, 369.

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