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Almost half of the RTX domain is dispensable for complement receptor 3 binding and cell-invasive activity of the Bordetella adenylate cyclase toxin
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SYSNO ASEP 0544756 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Almost half of the RTX domain is dispensable for complement receptor 3 binding and cell-invasive activity of the Bordetella adenylate cyclase toxin Author(s) Espinosa-Vinals, Carlos Angel (MBU-M)
Mašín, Jiří (MBU-M) RID, ORCID
Holubová, Jana (MBU-M) RID, ORCID
Staněk, Ondřej (MBU-M) RID, ORCID
Jurnečka, David (MBU-M) ORCID
Osička, Radim (MBU-M) RID, ORCID
Šebo, Peter (MBU-M) RID, ORCID
Bumba, Ladislav (MBU-M) RID, ORCIDArticle number 100833 Source Title Journal of Biological Chemistry. - : Elsevier - ISSN 0021-9258
Roč. 297, č. 1 (2021)Number of pages 13 s. Language eng - English Country US - United States Keywords identification ; translocation ; secretion ; acylation ; membrane ; delivery Subject RIV EE - Microbiology, Virology OECD category Microbiology R&D Projects GA19-15175S GA ČR - Czech Science Foundation (CSF) GA19-04607S GA ČR - Czech Science Foundation (CSF) GX19-27630X GA ČR - Czech Science Foundation (CSF) LM2018133 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) Method of publishing Open access Institutional support MBU-M - RVO:61388971 UT WOS 000678068400033 EID SCOPUS 85108681685 DOI 10.1016/j.jbc.2021.100833 Annotation The whooping cough agent Bordetella pertussis secretes an adenylate cyclase toxin (CyaA) that through its large carboxy-proximal Repeat-in-ToXin (RTX) domain binds the complement receptor 3 (CR3). The RTX domain consists of five blocks (I-V) of characteristic glycine and aspartate-rich nonapeptides that fold into five Ca2+-loaded parallel beta-rolls. Previous work indicated that the CR3-binding structure comprises the interface of beta-rolls II and III. To test if further portions of the RTX domain contribute to CR3 binding, we generated a construct with the RTX block II/III interface (CyaA residues 1132-1294) linked directly to the C-terminal block V fragment bearing the folding scaffold (CyaA residues 1562-1681). Despite deletion of 267 internal residues of the RTX domain, the Ca2+-driven folding of the hybrid block III/V beta-roll still supported formation of the CR3-binding structure at the interface of beta-rolls II and III. Moreover, upon stabilization by N- and C-terminal flanking segments, the block III/V hybrid-comprising constructs competed with CyaA for CR3 binding and induced formation of CyaA toxin-neutralizing antibodies in mice. Finally, a truncated CyaA.1295- 1561 toxin bound and penetrated erythrocytes and CR3-expressing cells, showing that the deleted portions of RTX blocks III, IV, and V (residues 1295-1561) were dispensable for CR3 binding and for toxin translocation across the target cell membrane. This suggests that almost a half of the RTX domain of CyaA is not involved in target cell interaction and rather serves the purpose of toxin secretion. Workplace Institute of Microbiology Contact Eliška Spurná, eliska.spurna@biomed.cas.cz, Tel.: 241 062 231 Year of Publishing 2022 Electronic address https://www.webofscience.com/wos/woscc/full-record/WOS:000678068400033
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