Skip to content
1887

Microbiology Society logo Microbiology

Volume 160, Issue 11

Variable processing of the IgA protease autotransporter at the cell surface of Free

Abstract

As with all classical monomeric autotransporters, IgA protease of is a modular protein consisting of an N-terminal signal sequence, a passenger domain and a C-terminal translocator domain (TD) that assists in the secretion of the passenger domain across the outer membrane. The passenger of IgA protease consists of three separate domains: the protease domain, the γ-peptide and the α-peptide that contains nuclear localization signals (NLSs). The protease domain is released into the extracellular milieu either via autocatalytic processing or via cleavage by another autotransporter, NalP, expression of which is phase-variable. NalP-mediated cleavage results in the release of a passenger that includes the α- and γ-peptides. Here, we studied the fate of the α-peptide when NalP was not expressed and observed strain-dependent differences. In meningococcal strains where the α-peptide contained a single NLS, the α-peptide remained covalently attached to the TD and was detected at the cell surface. In other strains, the α-peptide contained four NLSs and was separated from the TD by an IgA protease autoproteolytic cleavage site. In many of those cases, the α-peptide was found non-covalently associated with the cells as a separate polypeptide. The cell surface association of the α-peptides may be relevant physiologically. We report a novel function for the α-peptide, i.e. the binding of heparin – an immune-modulatory molecule that in the host is found in the extracellular matrix and connected to cell surfaces.

  • Received:
  • Accepted:
  • Published Online:
Funding
This study was supported by the:
  • Research Council for Chemical Sciences
  • Netherlands Organization for Scientific Research
  • Netherlands Organization for Health Research and Development
© Microbiology Society
Loading

Article metrics loading...

/content/journal/micro/10.1099/mic.0.082511-0
2014-11-01
2025-01-14
Loading full text...

Full text loading...

/deliver/fulltext/micro/160/11/2421.html?itemId=/content/journal/micro/10.1099/mic.0.082511-0&mimeType=html&fmt=ahah

References

  1. Arenas J., Nijland R., Rodriguez F. J., Bosma T. N. P., Tommassen J. ( 2013). Involvement of three meningococcal surface-exposed proteins, the heparin-binding protein NhbA, the α-peptide of IgA protease and the autotransporter protease NalP, in initiation of biofilm formation. Mol Microbiol 87:254–268 [View Article][PubMed]
     [Google Scholar]
  2. Bos M. P., Tommassen J. ( 2005). Viability of a capsule- and lipopolysaccharide-deficient mutant of Neisseria meningitidis . Infect Immun 73:6194–6197 [View Article][PubMed]
     [Google Scholar]
  3. Budroni S., Siena E., Dunning Hotopp J. C., Seib K. L., Serruto D., Nofroni C., Comanducci M., Riley D. R., Daugherty S. C. & other authors ( 2010). Neisseria meningitidis is structured in clades associated with restriction modification systems that modulate homologous recombination. Proc Natl Acad Sci U S A 108:4494–4499 [CrossRef]
     [Google Scholar]
  4. Celik N., Webb C. T., Leyton D. L., Holt K. E., Heinz E., Gorrell R., Kwok T., Naderer T., Strugnell R. A. & other authors ( 2012). A bioinformatic strategy for the detection, classification and analysis of bacterial autotransporters. PLoS ONE 7:e43245 [View Article][PubMed]
     [Google Scholar]
  5. Duensing T. D., Wing J. S., van Putten J. P. M. ( 1999). Sulfated polysaccharide-directed recruitment of mammalian host proteins: a novel strategy in microbial pathogenesis. Infect Immun 67:4463–4468[PubMed]
     [Google Scholar]
  6. Grijpstra J., Arenas J., Rutten L., Tommassen J. ( 2013). Autotransporter secretion: varying on a theme. Res Microbiol 164:562–582 [View Article][PubMed]
     [Google Scholar]
  7. Jain S., Goldberg M. B. ( 2007). Requirement for YaeT in the outer membrane assembly of autotransporter proteins. J Bacteriol 189:5393–5398 [View Article][PubMed]
     [Google Scholar]
  8. Jose J., Wölk U., Lorenzen D., Wenschuh H., Meyer T. F. ( 2000). Human T-cell response to meningococcal immunoglobulin A1 protease associated alpha-proteins. Scand J Immunol 51:176–185 [View Article][PubMed]
     [Google Scholar]
  9. Klauser T., Krämer J., Otzelberger K., Pohlner J., Meyer T. F. ( 1993). Characterization of the Neisseria Igaβ-core. The essential unit for outer membrane targeting and extracellular protein secretion. J Mol Biol 234:579–593 [View Article][PubMed]
     [Google Scholar]
  10. Konieczny M. P. J. enz I., Hollinderbäumer B., Beinke C., Niederweis M., Schmidt M. A. ( 2001). Modular organization of the AIDA autotransporter translocator: the N-terminal beta1-domain is surface-exposed and stabilizes the transmembrane beta2-domain. Antonie van Leeuwenhoek 80:19–34 [View Article][PubMed]
     [Google Scholar]
  11. Lappann M., Otto A., Becher D., Vogel U. ( 2013). Comparative proteome analysis of spontaneous outer membrane vesicles and purified outer membranes of Neisseria meningitidis . J Bacteriol 195:4425–4435 [View Article][PubMed]
     [Google Scholar]
  12. Menozzi F. D., Pethe K., Bifani P., Soncin F., Brennan M. J., Locht C. ( 2002). Enhanced bacterial virulence through exploitation of host glycosaminoglycans. Mol Microbiol 43:1379–1386 [View Article][PubMed]
     [Google Scholar]
  13. Oomen C. J., van Ulsen P., van Gelder P., Feijen M., Tommassen J., Gros P. ( 2004). Structure of the translocator domain of a bacterial autotransporter. EMBO J 23:1257–1266 [View Article][PubMed]
     [Google Scholar]
  14. Piet J. R., Huis in ’t Veld R. A., van Schaik B. D., van Kampen A. H., Baas F., van de Beek D., Pannekoek Y., van der Ende A. ( 2011). Genome sequence of Neisseria meningitidis serogroup B strain H44/76. J Bacteriol 193:2371–2372 [CrossRef]
     [Google Scholar]
  15. Pohlner J., Halter R., Beyreuther K., Meyer T. F. ( 1987). Gene structure and extracellular secretion of Neisseria gonorrhoeae IgA protease. Nature 325:458–462 [View Article][PubMed]
     [Google Scholar]
  16. Pohlner J., Langenberg U., Wölk U., Beck S. C., Meyer T. F. ( 1995). Uptake and nuclear transport of Neisseria IgA1 protease-associated alpha-proteins in human cells. Mol Microbiol 17:1073–1083 [View Article][PubMed]
     [Google Scholar]
  17. Poulsen K., Reinholdt J., Kilian M. ( 1992). A comparative genetic study of serologically distinct Haemophilus influenzae type 1 immunoglobulin A1 proteases. J Bacteriol 174:2913–2921[PubMed]
     [Google Scholar]
  18. Roussel-Jazédé V., Jongerius I., Bos M. P., Tommassen J., van Ulsen P. ( 2010). NalP-mediated proteolytic release of lactoferrin-binding protein B from the meningococcal cell surface. Infect Immun 78:3083–3089 [View Article][PubMed]
     [Google Scholar]
  19. Roussel-Jazédé V., Van Gelder P., Sijbrandi R., Rutten L., Otto B. R., Luirink J., Gros P., Tommassen J., Van Ulsen P. ( 2011). Channel properties of the translocator domain of the autotransporter Hbp of Escherichia coli . Mol Membr Biol 28:158–170 [View Article][PubMed]
     [Google Scholar]
  20. Roussel-Jazédé V., Grijpstra J., van Dam V., Tommassen J., van Ulsen P. ( 2013). Lipidation of the autotransporter NalP of Neisseria meningitidis is required for its function in the release of cell-surface-exposed proteins. Microbiology 159:286–295 [View Article][PubMed]
     [Google Scholar]
  21. Saurí A., Oreshkova N., Soprova Z., Jong W. S. P., Sani M., Peters P. J., Luirink J., van Ulsen P. ( 2011). Autotransporter β-domains have a specific function in protein secretion beyond outer-membrane targeting. J Mol Biol 412:553–567 [View Article][PubMed]
     [Google Scholar]
  22. Serruto D., Spadafina T., Ciucchi L., Lewis L. A., Ram S., Tontini M., Santini L., Biolchi A., Seib K. L. & other authors ( 2010). Neisseria meningitidis GNA2132, a heparin-binding protein that induces protective immunity in humans. Proc Natl Acad Sci U S A 107:3770–3775 [View Article][PubMed]
     [Google Scholar]
  23. Sievers F., Wilm A., Dineen D., Gibson T. J., Karplus K., Li W., Lopez R., McWilliam H., Remmert M. & other authors ( 2011). Fast, scalable generation of high-quality protein multiple sequence alignments using clustal Omega. Mol Syst Biol 7:539 [View Article][PubMed]
     [Google Scholar]
  24. van Ulsen P., Tommassen J. ( 2006). Protein secretion and secreted proteins in pathogenic Neisseriaceae . FEMS Microbiol Rev 30:292–319 [View Article][PubMed]
     [Google Scholar]
  25. van Ulsen P., van Alphen L., Hopman C. T. P., van der Ende A., Tommassen J. ( 2001). In vivo expression of Neisseria meningitidis proteins homologous to the Haemophilus influenzae Hap and Hia autotransporters. FEMS Immunol Med Microbiol 32:53–64 [View Article][PubMed]
     [Google Scholar]
  26. van Ulsen P., van Alphen L., ten Hove J., Fransen F., van der Ley P., Tommassen J. ( 2003). A Neisserial autotransporter NalP modulating the processing of other autotransporters. Mol Microbiol 50:1017–1030 [View Article][PubMed]
     [Google Scholar]
  27. van Ulsen P., Adler B., Fassler P., Gilbert M., van Schilfgaarde M., van der Ley P., van Alphen L., Tommassen J. ( 2006). A novel phase-variable autotransporter serine protease, AusI, of Neisseria meningitidis . Microbes Infect 8:2088–2097 [View Article][PubMed]
     [Google Scholar]
  28. van Ulsen P., Rahman S., Jong W. S., Daleke-Schermerhorn M. H., Luirink J. ( 2014). Type V secretion: from biogenesis to biotechnology. Biochim Biophys Acta 1843:1592–1611 [View Article][PubMed]
     [Google Scholar]
  29. Vidarsson G., Overbeeke N., Stemerding A. M., van den Dobbelsteen G., van Ulsen P., van der Ley P., Kilian M., van de Winkel J. G. J. ( 2005). Working mechanism of immunoglobulin A1 (IgA1) protease: cleavage of IgA1 antibody to Neisseria meningitidis PorA requires de novo synthesis of IgA1 protease. Infect Immun 73:6721–6726 [View Article][PubMed]
     [Google Scholar]
  30. Voulhoux R., Bos M. P., Geurtsen J., Mols M., Tommassen J. ( 2003). Role of a highly conserved bacterial protein in outer membrane protein assembly. Science 299:262–265 [View Article][PubMed]
     [Google Scholar]
  31. Yu H. N., Muñoz E. M., Edens R. E., Linhardt R. J. ( 2005). Kinetic studies on the interactions of heparin and complement proteins using surface plasmon resonance. Biochim Biophys Acta 1726:168–176 [View Article][PubMed]
     [Google Scholar]
/content/journal/micro/10.1099/mic.0.082511-0
Loading
Variable processing of the IgA protease autotransporter at the cell surface of Neisseria meningitidis
Microbiology 160, 2421 (2014); https://doi.org/10.1099/mic.0.082511-0
/content/journal/micro/10.1099/mic.0.082511-0
/content/journal/micro/10.1099/mic.0.082511-0
Loading

Data & Media loading...

Supplements

Supplementary material 1

PDF

Most cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error