Haemophilus influenzae protein E recognizes the C-terminal domain of vitronectin and modulates the membrane attack complex.
Singh, Birendra LU ; Jalalvand, Farshid LU ; Mörgelin, Matthias LU ; Zipfel, Peter ; Blom, Anna LU
and Riesbeck, Kristian
LU
(2011)
In Molecular Microbiology
81.
p.80-98
- Abstract
- Haemophilus influenzae protein E (PE) is a 16 kDa adhesin that induces a pro-inflammatory immune response in lung epithelial cells. The active epithelial binding region comprising amino acids PE 84-108 also interferes with complement-mediated bacterial killing by capturing vitronectin (Vn) that prevents complement deposition and formation of the membrane attack complex (MAC). Here, the interaction between PE and Vn was characterized using site-directed mutagenesis. Protein E variants were produced both in soluble forms and in surface-expressed molecules on Escherichia coli. Mutations within PE(84-108) in the full-length molecule revealed that K85 and R86 residues were important for the Vn binding. Bactericidal activity against H.... (More)
- Haemophilus influenzae protein E (PE) is a 16 kDa adhesin that induces a pro-inflammatory immune response in lung epithelial cells. The active epithelial binding region comprising amino acids PE 84-108 also interferes with complement-mediated bacterial killing by capturing vitronectin (Vn) that prevents complement deposition and formation of the membrane attack complex (MAC). Here, the interaction between PE and Vn was characterized using site-directed mutagenesis. Protein E variants were produced both in soluble forms and in surface-expressed molecules on Escherichia coli. Mutations within PE(84-108) in the full-length molecule revealed that K85 and R86 residues were important for the Vn binding. Bactericidal activity against H. influenzae was higher in human serum pre-treated with full-length PE as compared with serum incubated with PE(K85E, R86D) , suggesting that PE quenched Vn. A series of truncated Vn molecules revealed that the C-terminal domain comprising Vn(353-363) harboured the major binding region for PE. Interestingly, MAC deposition was significantly higher on mutants devoid of PE due to a decreased Vn-binding capacity when compared with wild-type H. influenzae. Our results define a fine-tuned interaction between H. influenzae and the innate immune system, and identify the mode of control of the MAC that is important for pathogen complement evasion. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1973173
- author
- Singh, Birendra
LU
; Jalalvand, Farshid
LU
; Mörgelin, Matthias
LU
; Zipfel, Peter
; Blom, Anna
LU
and Riesbeck, Kristian
LU
- organization
- publishing date
- 2011
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Molecular Microbiology
- volume
- 81
- pages
- 80 - 98
- publisher
- Wiley-Blackwell
- external identifiers
-
- wos:000292106200007
- pmid:21542857
- scopus:79959572234
- ISSN
- 1365-2958
- DOI
- 10.1111/j.1365-2958.2011.07678.x
- language
- English
- LU publication?
- yes
- id
- dd4b5446-600e-40c9-b7bd-dc5b91c4b59a (old id 1973173)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/21542857?dopt=Abstract
- date added to LUP
- 2016-04-04 08:50:14
- date last changed
- 2022-01-29 07:22:29
@article{dd4b5446-600e-40c9-b7bd-dc5b91c4b59a,
abstract = {{Haemophilus influenzae protein E (PE) is a 16 kDa adhesin that induces a pro-inflammatory immune response in lung epithelial cells. The active epithelial binding region comprising amino acids PE 84-108 also interferes with complement-mediated bacterial killing by capturing vitronectin (Vn) that prevents complement deposition and formation of the membrane attack complex (MAC). Here, the interaction between PE and Vn was characterized using site-directed mutagenesis. Protein E variants were produced both in soluble forms and in surface-expressed molecules on Escherichia coli. Mutations within PE(84-108) in the full-length molecule revealed that K85 and R86 residues were important for the Vn binding. Bactericidal activity against H. influenzae was higher in human serum pre-treated with full-length PE as compared with serum incubated with PE(K85E, R86D) , suggesting that PE quenched Vn. A series of truncated Vn molecules revealed that the C-terminal domain comprising Vn(353-363) harboured the major binding region for PE. Interestingly, MAC deposition was significantly higher on mutants devoid of PE due to a decreased Vn-binding capacity when compared with wild-type H. influenzae. Our results define a fine-tuned interaction between H. influenzae and the innate immune system, and identify the mode of control of the MAC that is important for pathogen complement evasion.}},
author = {{Singh, Birendra and Jalalvand, Farshid and Mörgelin, Matthias and Zipfel, Peter and Blom, Anna and Riesbeck, Kristian}},
issn = {{1365-2958}},
language = {{eng}},
pages = {{80--98}},
publisher = {{Wiley-Blackwell}},
series = {{Molecular Microbiology}},
title = {{Haemophilus influenzae protein E recognizes the C-terminal domain of vitronectin and modulates the membrane attack complex.}},
url = {{http://dx.doi.org/10.1111/j.1365-2958.2011.07678.x}},
doi = {{10.1111/j.1365-2958.2011.07678.x}},
volume = {{81}},
year = {{2011}},
}