Transmembrane segments of complement receptor 3 do not participate in cytotoxic activities but determine receptor structure required for action of Bordetella adenylate cyclase toxin

0460039 - MBÚ 2017 RIV GB eng J - Journal Article
Wald, Tomáš - Osičková, Adriana - Mašín, Jiří - Matyska Lišková, Petra - Petry-Podgórska, Inga - Matoušek, Tomáš - Šebo, Peter - Osička, Radim
Transmembrane segments of complement receptor 3 do not participate in cytotoxic activities but determine receptor structure required for action of Bordetella adenylate cyclase toxin.
Pathogens and Disease. Roč. 74, č. 3 (2016), flw008. ISSN 2049-632X. E-ISSN 2049-632X
R&D Projects: GA ČR(CZ) GAP302/11/0580; GA ČR GAP302/12/0460; GA ČR GA13-14547S
Institutional support: RVO:61388971 ; RVO:68081715
Keywords : adenylate cyclase toxin * ICP-MS * CD11b/CD18
Subject RIV: EE - Microbiology, Virology; CB - Analytical Chemistry, Separation (UIACH-O)
Impact factor: 2.335, year: 2016

Adenylate cyclase toxin-hemolysin (CyaA, ACT or AC-Hly) of the whooping cough agent Bordetella pertussis penetrates phagocytes expressing the integrin complement receptor 3 (CR3, CD11b/CD18, alpha(M)beta(2) or Mac-1). CyaA translocates its adenylate cyclase (AC) enzyme domain into cell cytosol and catalyzes unregulated conversion of ATP to cAMP, thereby subverting cellular signaling. In parallel, CyaA forms small cation-selective membrane pores that permeabilize cells for potassium efflux, contributing to cytotoxicity of CyaA and eventually provoking colloid-osmotic cell lysis. To investigate whether the single-pass alpha-helical transmembrane segments of CR3 subunits CD11b and CD18 do directly participate in AC domain translocation and/or pore formation by the toxin, we expressed in CHO cells variants of CR3 that contained artificial transmembrane segments, or lacked the transmembrane segment(s) at all. The results demonstrate that the transmembrane segments of CR3 are not directly involved in the cytotoxic activities of CyaA but serve for maintaining CR3 in a conformation that is required for efficient toxin binding and action.
Permanent Link: http://hdl.handle.net/11104/0260188