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Membrane-Active Properties of an Amphitropic Peptide from the CyaA Toxin Translocation Region
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...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5705984/ https://www.ncbi.nlm.nih.gov/pubmed/29135925 http://dx.doi.org/10.3390/toxins9110369 |
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author | Voegele, Alexis Subrini, Orso Sapay, Nicolas Ladant, Daniel Chenal, Alexandre |
author_facet | Voegele, Alexis Subrini, Orso Sapay, Nicolas Ladant, Daniel Chenal, Alexandre |
author_sort | Voegele, Alexis |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-5705984 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-57059842017-12-04 Membrane-Active Properties of an Amphitropic Peptide from the CyaA Toxin Translocation Region Voegele, Alexis Subrini, Orso Sapay, Nicolas Ladant, Daniel Chenal, Alexandre Toxins (Basel) Article 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. MDPI 2017-11-14 /pmc/articles/PMC5705984/ /pubmed/29135925 http://dx.doi.org/10.3390/toxins9110369 Text en © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Voegele, Alexis Subrini, Orso Sapay, Nicolas Ladant, Daniel Chenal, Alexandre Membrane-Active Properties of an Amphitropic Peptide from the CyaA Toxin Translocation Region |
title | Membrane-Active Properties of an Amphitropic Peptide from the CyaA Toxin Translocation Region |
title_full | Membrane-Active Properties of an Amphitropic Peptide from the CyaA Toxin Translocation Region |
title_fullStr | Membrane-Active Properties of an Amphitropic Peptide from the CyaA Toxin Translocation Region |
title_full_unstemmed | Membrane-Active Properties of an Amphitropic Peptide from the CyaA Toxin Translocation Region |
title_short | Membrane-Active Properties of an Amphitropic Peptide from the CyaA Toxin Translocation Region |
title_sort | membrane-active properties of an amphitropic peptide from the cyaa toxin translocation region |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5705984/ https://www.ncbi.nlm.nih.gov/pubmed/29135925 http://dx.doi.org/10.3390/toxins9110369 |
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