title: Interaction of Bordetella adenylate cyclase toxin with complement receptor 3 involves multivalent glycan binding.
abstract: The interaction of Bordetella pertussis adenylate cyclase toxin (CyaA) with complement receptor 3 (CR3, CD11b/CD18) involves N-linked oligosaccharide chains. To investigate the relative importance of the individual N-glycans of CR3 for toxin activity, the asparagine residues of the consensus N-glycosylation sites of CR3 were substituted with glutamine residues that cannot be glycosylated. Examination of CR3 mutant variants and mass spectrometry analysis of the N-glycosylation pattern of CR3 revealed that N-glycans located in the C-terminal part of the CD11b subunit are involved in binding and cytotoxic activity of CyaA. We suggest that these N-glycans form a defined clustered saccharide patch that enables multivalent contact of CR3 with CyaA, enhancing both affinity and specificity of the integrin-toxin interaction.
authors.affiliation: Institute of Microbiology, Academy of Sciences of the Czech Republic, v.v.i., Videnska 1083, 142 20 Prague 4, Czech Republic.
authors.forename: Shakir
authors.initials: S
authors.lastname: Hasan
authors.affiliation: Institute of Microbiology, Academy of Sciences of the Czech Republic, v.v.i., Videnska 1083, 142 20 Prague 4, Czech Republic; Department of Biochemistry, Faculty of Science, Charles University in Prague, Hlavova 8, 128 43 Prague 2, Czech Republic.
authors.forename: Adriana
authors.initials: A
authors.lastname: Osickova
authors.affiliation: Institute of Microbiology, Academy of Sciences of the Czech Republic, v.v.i., Videnska 1083, 142 20 Prague 4, Czech Republic.
authors.forename: Ladislav
authors.initials: L
authors.lastname: Bumba
authors.affiliation: Institute of Microbiology, Academy of Sciences of the Czech Republic, v.v.i., Videnska 1083, 142 20 Prague 4, Czech Republic.
authors.forename: Petr
authors.initials: P
authors.lastname: Novák
authors.affiliation: Institute of Microbiology, Academy of Sciences of the Czech Republic, v.v.i., Videnska 1083, 142 20 Prague 4, Czech Republic.
authors.forename: Peter
authors.initials: P
authors.lastname: Sebo
authors.affiliation: Institute of Microbiology, Academy of Sciences of the Czech Republic, v.v.i., Videnska 1083, 142 20 Prague 4, Czech Republic. Electronic address: osicka@biomed.cas.cz.
authors.forename: Radim
authors.initials: R
authors.lastname: Osicka
mesh_terms: D037361:Adenylate Cyclase Toxin / Q000235:genetics / Q000378:metabolism*; D019943:Amino Acid Substitution; D001216:Asparagine / Q000235:genetics; D001886:Bordetella pertussis / Q000378:metabolism / Q000472:pathogenicity; D039481:CD11b Antigen / Q000737:chemistry / Q000378:metabolism*; D018821:CD18 Antigens / Q000737:chemistry / Q000378:metabolism*; D005973:Glutamine / Q000235:genetics; D006031:Glycosylation; D006801:Humans; D016177:Macrophage-1 Antigen / Q000235:genetics / Q000378:metabolism*; D011134:Polysaccharides / Q000378:metabolism*; D017434:Protein Structure, Tertiary
chemical_list: D037361:Adenylate Cyclase Toxin; D039481:CD11b Antigen; D018821:CD18 Antigens; D016177:Macrophage-1 Antigen; D011134:Polysaccharides; D005973:Glutamine; D001216:Asparagine
keywords: Adenylate cyclase toxin; CD11b/CD18; Complement receptor type 3; N-linked glycosylation; Point mutants; Repeats in toxin