Interaction of Bordetella pertussis adenylate cyclase with CD11b/CD18: Role of toxin acylation and identification of the main integrin interaction domain.
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 alphaMbeta2 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.
El-Azami-El-Idrissi
Mohammed
M
Unité de Biologie des Régulations Immunitaires, INSERM E 0352, Institut Pasteur, 75724 Paris, France.
Bauche
Cécile
C
Loucka
Jirina
J
Osicka
Radim
R
Sebo
Peter
P
Ladant
Daniel
D
Leclerc
Claude
C
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry; D001224:Aspartic Acid / Q000737:chemistry; D001710:Biotin / Q000494:pharmacology; D001886:Bordetella pertussis / Q000201:enzymology*; D039481:CD11b Antigen / Q000378:metabolism*; D018821:CD18 Antigens / Q000378:metabolism*; D016466:CHO Cells; D002469:Cell Separation; D006224:Cricetinae; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000378:metabolism; D004926:Escherichia coli / Q000378:metabolism; D005434:Flow Cytometry; D005822:Genetic Vectors; D005998:Glycine / Q000737:chemistry; D006801:Humans; D016023:Integrins / Q000737:chemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000378:metabolism; D012756:Sheep; D014118:Toxins, Biological / Q000737:chemistry; D014162:Transfection
D000911:Antibodies, Monoclonal; D039481:CD11b Antigen; D018821:CD18 Antigens; D016023:Integrins; D011994:Recombinant Proteins; D014118:Toxins, Biological; D001224:Aspartic Acid; D001710:Biotin; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D005998:Glycine