Bordetella adenylate cyclase toxin is a unique ligand of the integrin complement receptor 3

0456423 - MBÚ 2016 RIV GB eng J - Journal Article
Osička, Radim - Osičková, Adriana - Hasan, Shakir - Bumba, Ladislav - Černý, Jiří - Šebo, Peter
Bordetella adenylate cyclase toxin is a unique ligand of the integrin complement receptor 3.
eLife. Roč. 4, DEC 9 (2015). ISSN 2050-084X. E-ISSN 2050-084X
R&D Projects: GA ČR(CZ) GAP302/11/0580; GA ČR(CZ) GA15-11851S; GA MŠMT(CZ) ED1.1.00/02.0109
Institutional support: RVO:61388971 ; RVO:86652036
Keywords : E. coli * adenylate cyclase toxin * biochemistry
Subject RIV: CE - Biochemistry
Impact factor: 8.282, year: 2015

Integrins are heterodimeric cell surface adhesion and signaling receptors that are essential for metazoan existence. Some integrins contain an I-domain that is a major ligand binding site. The ligands preferentially engage the active forms of the integrins and trigger signaling cascades that alter numerous cell functions. Here we found that the adenylate cyclase toxin (CyaA), a key virulence factor of the whooping cough agent Bordetella pertussis, preferentially binds an inactive form of the integrin complement receptor 3 (CR3), using a site outside of its I-domain. CyaA binding did not trigger downstream signaling of CR3 in human monocytes and CyaAcatalyzed elevation of cAMP effectively blocked CR3 signaling initiated by a natural ligand. This unprecedented type of integrin-ligand interaction distinguishes CyaA from all other known ligands of the I-domain-containing integrins and provides a mechanistic insight into the previously observed central role of CyaA in the pathogenesis of B. pertussis.
Permanent Link: http://hdl.handle.net/11104/0256952