Yersinia pestis Ail recruitment of C4b-binding protein leads to factor I- mediated inactivation of covalently and noncovalently bound C4b
Ho, Derek K. ; Skurnik, Mikael ; Blom, Anna LU
and Meri, Seppo
(2014)
In European Journal of Immunology
44(3).
p.742-751
- Abstract
- The outer membrane protein Ail of Yersinia pestis mediates several virulence functions, including serum resistance. Here, we demonstrate that Ail binds C4b-binding protein (C4BP), the primary fluid-phase regulator of the classical and lectin pathways. Non-covalent binding of C4 and C4b to Ail was also observed. C4BP bound to Ail can act as a cofactor to the serine protease factor I (fI) in the cleavage of fluid-phase C4b. Employing a panel of C4BP alpha-chain mutants, we observed that the absence of complement control protein domain 6 and 8 reduced binding to Ail. Immunoblot analysis of normal human serum (NHS)-treated bacteria revealed minimal C4b alpha'-chain complexes with bacterial outer membrane targets. Addition of the anti-C4BP... (More)
- The outer membrane protein Ail of Yersinia pestis mediates several virulence functions, including serum resistance. Here, we demonstrate that Ail binds C4b-binding protein (C4BP), the primary fluid-phase regulator of the classical and lectin pathways. Non-covalent binding of C4 and C4b to Ail was also observed. C4BP bound to Ail can act as a cofactor to the serine protease factor I (fI) in the cleavage of fluid-phase C4b. Employing a panel of C4BP alpha-chain mutants, we observed that the absence of complement control protein domain 6 and 8 reduced binding to Ail. Immunoblot analysis of normal human serum (NHS)-treated bacteria revealed minimal C4b alpha'-chain complexes with bacterial outer membrane targets. Addition of the anti-C4BP monoclonal antibody MK104 to NHS restored C4b-alpha' chain target complexes, suggesting that C4b binds covalently to targets on the Y. pestis surface. C4b bound to Ail noncovalently was also cleaved in a C4BP and fI-dependent manner, leaving the C4c fragment bound to Ail. MK104 also prevented the cleavage of noncovalently bound C4b. Collectively, these data suggest that when C4BP is bound to Ail, fI can cleave and inactivate C4b that has bound covalently to bacterial surface structures as well as C4b bound noncovalently to Ail. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/4439912
- author
- Ho, Derek K.
; Skurnik, Mikael
; Blom, Anna
LU
and Meri, Seppo
- organization
- publishing date
- 2014
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Ail, C4b-binding protein, Complement, Yersinia
- in
- European Journal of Immunology
- volume
- 44
- issue
- 3
- pages
- 742 - 751
- publisher
- John Wiley & Sons Inc.
- external identifiers
-
- wos:000332933200016
- scopus:84896050071
- pmid:24760758
- ISSN
- 1521-4141
- DOI
- 10.1002/eji.201343552
- language
- English
- LU publication?
- yes
- id
- 9d26f66f-595b-4a28-afda-889b4a7e383b (old id 4439912)
- date added to LUP
- 2016-04-01 10:14:57
- date last changed
- 2022-01-25 21:22:26
@article{9d26f66f-595b-4a28-afda-889b4a7e383b,
abstract = {{The outer membrane protein Ail of Yersinia pestis mediates several virulence functions, including serum resistance. Here, we demonstrate that Ail binds C4b-binding protein (C4BP), the primary fluid-phase regulator of the classical and lectin pathways. Non-covalent binding of C4 and C4b to Ail was also observed. C4BP bound to Ail can act as a cofactor to the serine protease factor I (fI) in the cleavage of fluid-phase C4b. Employing a panel of C4BP alpha-chain mutants, we observed that the absence of complement control protein domain 6 and 8 reduced binding to Ail. Immunoblot analysis of normal human serum (NHS)-treated bacteria revealed minimal C4b alpha'-chain complexes with bacterial outer membrane targets. Addition of the anti-C4BP monoclonal antibody MK104 to NHS restored C4b-alpha' chain target complexes, suggesting that C4b binds covalently to targets on the Y. pestis surface. C4b bound to Ail noncovalently was also cleaved in a C4BP and fI-dependent manner, leaving the C4c fragment bound to Ail. MK104 also prevented the cleavage of noncovalently bound C4b. Collectively, these data suggest that when C4BP is bound to Ail, fI can cleave and inactivate C4b that has bound covalently to bacterial surface structures as well as C4b bound noncovalently to Ail.}},
author = {{Ho, Derek K. and Skurnik, Mikael and Blom, Anna and Meri, Seppo}},
issn = {{1521-4141}},
keywords = {{Ail; C4b-binding protein; Complement; Yersinia}},
language = {{eng}},
number = {{3}},
pages = {{742--751}},
publisher = {{John Wiley & Sons Inc.}},
series = {{European Journal of Immunology}},
title = {{Yersinia pestis Ail recruitment of C4b-binding protein leads to factor I- mediated inactivation of covalently and noncovalently bound C4b}},
url = {{http://dx.doi.org/10.1002/eji.201343552}},
doi = {{10.1002/eji.201343552}},
volume = {{44}},
year = {{2014}},
}