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The pH-regulated Antigen 1 of Candida albicans Binds the Human Complement Inhibitor C4b-binding Protein and Mediates Fungal Complement Evasion

Luo, Shanshan; Blom, Anna LU ; Rupp, Steffen; Hipler, Uta-Christina; Hube, Bernhard; Skerka, Christine and Zipfel, Peter F. (2011) In Journal of Biological Chemistry 286(10). p.8021-8029
Abstract
Candida albicans binds and utilizes human complement inhibitors, such as C4b-binding protein (C4BP), Factor H, and FHL-1 for immune evasion. Here, we identify Candida pH-regulated antigen 1 (Pra1) as the first fungal C4BP-binding protein. Recombinant Pra1 binds C4BP, as shown by ELISA and isothermal titration calorimetry, and the Pra1-C4BP interaction is ionic in nature. The Pra1 binding domains within C4BP were localized to the complement control protein domain 4 (CCP4), CCP7, and CCP8. C4BP bound to Pra1 maintains complement-inhibitory activity. C4BP and Factor H bind simultaneously to Candida Pra1 and do not compete for binding at physiological levels. A Pra1-overexpressing C. albicans strain, which had about 2-fold Pra1 levels at the... (More)
Candida albicans binds and utilizes human complement inhibitors, such as C4b-binding protein (C4BP), Factor H, and FHL-1 for immune evasion. Here, we identify Candida pH-regulated antigen 1 (Pra1) as the first fungal C4BP-binding protein. Recombinant Pra1 binds C4BP, as shown by ELISA and isothermal titration calorimetry, and the Pra1-C4BP interaction is ionic in nature. The Pra1 binding domains within C4BP were localized to the complement control protein domain 4 (CCP4), CCP7, and CCP8. C4BP bound to Pra1 maintains complement-inhibitory activity. C4BP and Factor H bind simultaneously to Candida Pra1 and do not compete for binding at physiological levels. A Pra1-overexpressing C. albicans strain, which had about 2-fold Pra1 levels at the surface acquired also about 2-fold C4BP to the surface, compared with the wild type strain CAI4. A Pra1 knock-out strain showed similar to 22% reduced C4BP binding. C4BP captured by C. albicans from human serum inhibits C4b and C3b surface deposition and also maintains cofactor activity. In summary, Candida Pra1 represents the first fungal C4BP-binding surface protein. Pra1, via binding to C4BP, mediates human complement control, thereby favoring the immune and complement evasion of C. albicans. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Biological Chemistry
volume
286
issue
10
pages
8021 - 8029
publisher
ASBMB
external identifiers
  • wos:000288013300033
  • scopus:79953136593
ISSN
1083-351X
DOI
10.1074/jbc.M110.130138
language
English
LU publication?
yes
id
53991772-634e-48ac-b8d5-9b9ae0fc6dfa (old id 1868373)
date added to LUP
2011-04-04 11:19:04
date last changed
2017-07-02 03:08:07
@article{53991772-634e-48ac-b8d5-9b9ae0fc6dfa,
  abstract     = {Candida albicans binds and utilizes human complement inhibitors, such as C4b-binding protein (C4BP), Factor H, and FHL-1 for immune evasion. Here, we identify Candida pH-regulated antigen 1 (Pra1) as the first fungal C4BP-binding protein. Recombinant Pra1 binds C4BP, as shown by ELISA and isothermal titration calorimetry, and the Pra1-C4BP interaction is ionic in nature. The Pra1 binding domains within C4BP were localized to the complement control protein domain 4 (CCP4), CCP7, and CCP8. C4BP bound to Pra1 maintains complement-inhibitory activity. C4BP and Factor H bind simultaneously to Candida Pra1 and do not compete for binding at physiological levels. A Pra1-overexpressing C. albicans strain, which had about 2-fold Pra1 levels at the surface acquired also about 2-fold C4BP to the surface, compared with the wild type strain CAI4. A Pra1 knock-out strain showed similar to 22% reduced C4BP binding. C4BP captured by C. albicans from human serum inhibits C4b and C3b surface deposition and also maintains cofactor activity. In summary, Candida Pra1 represents the first fungal C4BP-binding surface protein. Pra1, via binding to C4BP, mediates human complement control, thereby favoring the immune and complement evasion of C. albicans.},
  author       = {Luo, Shanshan and Blom, Anna and Rupp, Steffen and Hipler, Uta-Christina and Hube, Bernhard and Skerka, Christine and Zipfel, Peter F.},
  issn         = {1083-351X},
  language     = {eng},
  number       = {10},
  pages        = {8021--8029},
  publisher    = {ASBMB},
  series       = {Journal of Biological Chemistry},
  title        = {The pH-regulated Antigen 1 of Candida albicans Binds the Human Complement Inhibitor C4b-binding Protein and Mediates Fungal Complement Evasion},
  url          = {http://dx.doi.org/10.1074/jbc.M110.130138},
  volume       = {286},
  year         = {2011},
}