Originally published In Press as doi:10.1074/jbc.M304387200 on July 31, 2003
Originally published In Press as doi:10.1074/jbc.M304387200 on July 28, 2003
J. Biol. Chem., Vol. 278, Issue 40, 38514-38521, October 3, 2003
Interaction of Bordetella pertussis Adenylate Cyclase with CD11b/CD18
ROLE OF TOXIN ACYLATION AND IDENTIFICATION OF THE MAIN INTEGRIN INTERACTION DOMAIN*
Mohammed El-Azami-El-Idrissi
,
Cécile Bauche
,
Jirina Loucka ¶,
Radim Osicka ¶,
Peter Sebo ¶,
Daniel Ladant
and
Claude Leclerc
||
From the
Unité de Biologie des Régulations Immunitaires, INSERM E 0352, Institut Pasteur, 75724 Paris,
Unité de Biochimie des Interactions Macromoléculaires, CNRS URA 2185, Institut Pasteur, 75724 Paris, France, and the ¶Academy of Sciences of the Czech Republic, Videnska 1083, 142 20 Prague 4, Czech Republic
Adenylate cyclase toxin (CyaA) is one of the major virulence factors produced by Bordetella pertussis, the whooping cough agent. CyaA belongs to the repeat in toxin protein family and requires a post-translational fatty acylation to form cation-selective channels in target cell membranes and to penetrate into cytosol. We have demonstrated recently that CyaA uses the
M
2 integrin (CD11b/CD18) as a specific cellular receptor. Here we show that the acylation of CyaA is required for a productive and tight interaction of the toxin with cells expressing CD11b. In addition, we demonstrate that the catalytic domain is not required for binding of CyaA to CD11b and that the main integrin interacting domain of CyaA is located in its glycine/aspartate-rich repeat region. These data decipher, for the first time, the interaction of CyaA with CD11b-positive cells and open new prospects for understanding the interaction of Bordetella pertussis with innate and adaptive immune systems.
Received for publication, April 28, 2003
, and in revised form, July 24, 2003.
* This work was supported by the Pasteur Institute, ANRS, INSERM, CNRS (URA 2185), Grant QLK2-CT-1999-00556 from the 5th Framework Program of the European Union, by Czech Grants 310/01/0934 and A502907, and by National Institutes of Health Grant 55000334 from Howard Hughes Medical Institute (to P. S.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
|| To whom correspondence should be addressed: Unité de Biologie des Régulations Immunitaires, Institut Pasteur, 25 Rue du Dr Roux, 75724 Paris Cedex 15, France. Tel.: 33 1 45 68 86 18; Fax: 33 1 45 68 85 40; E-mail: cleclerc{at}pasteur.fr.

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Copyright © 2003 by the American Society for Biochemistry and Molecular Biology.