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Functional Recruitment of the Human Complement Inhibitor C4BP to Yersinia pseudotuberculosis Outer Membrane Protein Ail

Ho, Derek K.; Riva, Rauna; Kirjavainen, Vesa; Jarva, Hanna; Ginstrom, Erica; Blom, Anna LU ; Skurnik, Mikael and Meri, Seppo (2012) In Journal of Immunology 188(9). p.4450-4459
Abstract
All is a 17-kDa chromosomally encoded outer membrane protein that mediates serum resistance (complement resistance) in the pathogenic Yersiniae (Yersinia pestis, Y. enterocolitica, and Y. pseudotuberculosis). In this article, we demonstrate that Y pseudotuberculosis Ail from strains PB1, 2812/79, and YPIII/pIB1 (serotypes O:1a, O:1b, and O:3, respectively) can bind the inhibitor of the classical and lectin pathways of complement, C4b-binding protein (C4BP). Binding was observed irrespective of serotype tested and independently of YadA, which is the primary C4BP receptor of Y. enterocolitica. Disruption of the a gene in Y. pseudotuberculosis resulted in loss of C4BP binding. Cofactor assays revealed that bound C4BP is functional, because... (More)
All is a 17-kDa chromosomally encoded outer membrane protein that mediates serum resistance (complement resistance) in the pathogenic Yersiniae (Yersinia pestis, Y. enterocolitica, and Y. pseudotuberculosis). In this article, we demonstrate that Y pseudotuberculosis Ail from strains PB1, 2812/79, and YPIII/pIB1 (serotypes O:1a, O:1b, and O:3, respectively) can bind the inhibitor of the classical and lectin pathways of complement, C4b-binding protein (C4BP). Binding was observed irrespective of serotype tested and independently of YadA, which is the primary C4BP receptor of Y. enterocolitica. Disruption of the a gene in Y. pseudotuberculosis resulted in loss of C4BP binding. Cofactor assays revealed that bound C4BP is functional, because bound C4BP in the presence of factor I cleaved C4b. In the absence of YadA, Ail conferred serum resistance to strains PB1 and YPIII, whereas serum resistance was observed in strain 2812/79 in the absence of both YadA and Ail, suggesting additional serum resistance factors. Ail from strain YPIII/pIB1 alone can mediate serum resistance and C4BP binding, because its expression in a serum-sensitive laboratory strain of Escherichia coli conferred both of these phenotypes. Using a panel of C4BP mutants, each deficient in a single complement control protein domain, we observed that complement control protein domains 6-8 are important for binding to Ail. Binding of C4BP was unaffected by increasing heparin or salt concentrations, suggesting primarily nonionic interactions. These results indicate that Y. pseudotuberculosis Ail recruits C4BP in a functional manner, facilitating resistance to attack from complement. The Journal of Immunology, 2012, 188: 4450-4459. (Less)
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author
organization
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Contribution to journal
publication status
published
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in
Journal of Immunology
volume
188
issue
9
pages
4450 - 4459
publisher
American Association of Immunologists
external identifiers
  • wos:000303299900038
  • scopus:84860316450
ISSN
1550-6606
DOI
10.4049/jimmunol.1103149
language
English
LU publication?
yes
id
bea94a8a-59c4-431a-90a8-91ab359d52a1 (old id 2551709)
date added to LUP
2012-06-01 08:46:44
date last changed
2017-04-09 03:53:53
@article{bea94a8a-59c4-431a-90a8-91ab359d52a1,
  abstract     = {All is a 17-kDa chromosomally encoded outer membrane protein that mediates serum resistance (complement resistance) in the pathogenic Yersiniae (Yersinia pestis, Y. enterocolitica, and Y. pseudotuberculosis). In this article, we demonstrate that Y pseudotuberculosis Ail from strains PB1, 2812/79, and YPIII/pIB1 (serotypes O:1a, O:1b, and O:3, respectively) can bind the inhibitor of the classical and lectin pathways of complement, C4b-binding protein (C4BP). Binding was observed irrespective of serotype tested and independently of YadA, which is the primary C4BP receptor of Y. enterocolitica. Disruption of the a gene in Y. pseudotuberculosis resulted in loss of C4BP binding. Cofactor assays revealed that bound C4BP is functional, because bound C4BP in the presence of factor I cleaved C4b. In the absence of YadA, Ail conferred serum resistance to strains PB1 and YPIII, whereas serum resistance was observed in strain 2812/79 in the absence of both YadA and Ail, suggesting additional serum resistance factors. Ail from strain YPIII/pIB1 alone can mediate serum resistance and C4BP binding, because its expression in a serum-sensitive laboratory strain of Escherichia coli conferred both of these phenotypes. Using a panel of C4BP mutants, each deficient in a single complement control protein domain, we observed that complement control protein domains 6-8 are important for binding to Ail. Binding of C4BP was unaffected by increasing heparin or salt concentrations, suggesting primarily nonionic interactions. These results indicate that Y. pseudotuberculosis Ail recruits C4BP in a functional manner, facilitating resistance to attack from complement. The Journal of Immunology, 2012, 188: 4450-4459.},
  author       = {Ho, Derek K. and Riva, Rauna and Kirjavainen, Vesa and Jarva, Hanna and Ginstrom, Erica and Blom, Anna and Skurnik, Mikael and Meri, Seppo},
  issn         = {1550-6606},
  language     = {eng},
  number       = {9},
  pages        = {4450--4459},
  publisher    = {American Association of Immunologists},
  series       = {Journal of Immunology},
  title        = {Functional Recruitment of the Human Complement Inhibitor C4BP to Yersinia pseudotuberculosis Outer Membrane Protein Ail},
  url          = {http://dx.doi.org/10.4049/jimmunol.1103149},
  volume       = {188},
  year         = {2012},
}