The Choline-binding Protein PspC of Streptococcus pneumoniae Interacts with the C-terminal Heparin-binding Domain of Vitronectin
Voss, Sylvia ; Hallstroem, Teresia ; Saleh, Malek ; Burchhardt, Gerhard ; Pribyl, Thomas ; Singh, Birendra LU ; Riesbeck, Kristian LU
; Zipfel, Peter F.
and Hammerschmidt, Sven
(2013)
In Journal of Biological Chemistry
288(22).
p.15614-15627
- Abstract
- Adherence of Streptococcus pneumoniae is directly mediated by interactions of adhesins with eukaryotic cellular receptors or indirectly by exploiting matrix and serum proteins as molecular bridges. Pneumococci engage vitronectin, the human adhesive glycoprotein and complement inhibitor, to facilitate attachment to epithelial cells of the mucosal cavity, thereby modulating host cell signaling. In this study, we identified PspC as a vitronectin-binding protein interacting with the C-terminal heparin-binding domain of vitronectin. PspC is a multifunctional surface-exposed choline-binding protein displaying various adhesive properties. Vitronectin binding required the R domains in the mature PspC protein, which are also essential for the... (More)
- Adherence of Streptococcus pneumoniae is directly mediated by interactions of adhesins with eukaryotic cellular receptors or indirectly by exploiting matrix and serum proteins as molecular bridges. Pneumococci engage vitronectin, the human adhesive glycoprotein and complement inhibitor, to facilitate attachment to epithelial cells of the mucosal cavity, thereby modulating host cell signaling. In this study, we identified PspC as a vitronectin-binding protein interacting with the C-terminal heparin-binding domain of vitronectin. PspC is a multifunctional surface-exposed choline-binding protein displaying various adhesive properties. Vitronectin binding required the R domains in the mature PspC protein, which are also essential for the interaction with the ectodomain of the polymeric immunoglobulin receptor and secretory IgA. Consequently, secretory IgA competitively inhibited binding of vitronectin to purified PspC and to PspC-expressing pneumococci. In contrast, Factor H, which binds to the N-terminal part of mature PspC molecules, did not interfere with the PspC-vitronectin interaction. Using a series of vitronectin peptides, the C-terminal heparin-binding domain was shown to be essential for the interaction of soluble vitronectin with PspC. Binding experiments with immobilized vitronectin suggested a region N-terminal to the identified heparin-binding domain as an additional binding region for PspC, suggesting that soluble, immobilized, as well as cellularly bound vitronectin possesses different conformations. Finally, vitronectin bound to PspC was functionally active and inhibited the deposition of the terminal complement complex. In conclusion, this study identifies and characterizes (on the molecular level) the interaction between the pneumococcal adhesin PspC and the human glycoprotein vitronectin. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/3927246
- author
- Voss, Sylvia
; Hallstroem, Teresia
; Saleh, Malek
; Burchhardt, Gerhard
; Pribyl, Thomas
; Singh, Birendra
LU
; Riesbeck, Kristian
LU
; Zipfel, Peter F.
and Hammerschmidt, Sven
- organization
- publishing date
- 2013
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Biological Chemistry
- volume
- 288
- issue
- 22
- pages
- 15614 - 15627
- publisher
- American Society for Biochemistry and Molecular Biology
- external identifiers
-
- wos:000319822300019
- scopus:84878392079
- pmid:23603906
- ISSN
- 1083-351X
- DOI
- 10.1074/jbc.M112.443507
- language
- English
- LU publication?
- yes
- id
- 7766c10c-36d3-4d43-977b-7f606dfe87fc (old id 3927246)
- date added to LUP
- 2016-04-01 10:51:55
- date last changed
- 2022-04-12 18:18:38
@article{7766c10c-36d3-4d43-977b-7f606dfe87fc,
abstract = {{Adherence of Streptococcus pneumoniae is directly mediated by interactions of adhesins with eukaryotic cellular receptors or indirectly by exploiting matrix and serum proteins as molecular bridges. Pneumococci engage vitronectin, the human adhesive glycoprotein and complement inhibitor, to facilitate attachment to epithelial cells of the mucosal cavity, thereby modulating host cell signaling. In this study, we identified PspC as a vitronectin-binding protein interacting with the C-terminal heparin-binding domain of vitronectin. PspC is a multifunctional surface-exposed choline-binding protein displaying various adhesive properties. Vitronectin binding required the R domains in the mature PspC protein, which are also essential for the interaction with the ectodomain of the polymeric immunoglobulin receptor and secretory IgA. Consequently, secretory IgA competitively inhibited binding of vitronectin to purified PspC and to PspC-expressing pneumococci. In contrast, Factor H, which binds to the N-terminal part of mature PspC molecules, did not interfere with the PspC-vitronectin interaction. Using a series of vitronectin peptides, the C-terminal heparin-binding domain was shown to be essential for the interaction of soluble vitronectin with PspC. Binding experiments with immobilized vitronectin suggested a region N-terminal to the identified heparin-binding domain as an additional binding region for PspC, suggesting that soluble, immobilized, as well as cellularly bound vitronectin possesses different conformations. Finally, vitronectin bound to PspC was functionally active and inhibited the deposition of the terminal complement complex. In conclusion, this study identifies and characterizes (on the molecular level) the interaction between the pneumococcal adhesin PspC and the human glycoprotein vitronectin.}},
author = {{Voss, Sylvia and Hallstroem, Teresia and Saleh, Malek and Burchhardt, Gerhard and Pribyl, Thomas and Singh, Birendra and Riesbeck, Kristian and Zipfel, Peter F. and Hammerschmidt, Sven}},
issn = {{1083-351X}},
language = {{eng}},
number = {{22}},
pages = {{15614--15627}},
publisher = {{American Society for Biochemistry and Molecular Biology}},
series = {{Journal of Biological Chemistry}},
title = {{The Choline-binding Protein PspC of Streptococcus pneumoniae Interacts with the C-terminal Heparin-binding Domain of Vitronectin}},
url = {{https://lup.lub.lu.se/search/files/2197455/4147042.pdf}},
doi = {{10.1074/jbc.M112.443507}},
volume = {{288}},
year = {{2013}},
}