Fine Mapping of the Interaction between C4b-Binding Protein and Outer Membrane Proteins LigA and LigB of Pathogenic Leptospira interrogans.
Breda, Leandro C D ; Hsieh, Ching-Lin ; Castiblanco Valencia, Mónica M ; da Silva, Ludmila B ; Barbosa, Angela S ; Blom, Anna LU
; Yung-Fu, Chang
and Isaac, Lourdes
(2015)
In PLoS Neglected Tropical Diseases
9(10).
- Abstract
- The complement system consists of more than 40 proteins that participate in the inflammatory response and in pathogen killing. Complement inhibitors are necessary to avoid the excessive consumption and activation of this system on host cells. Leptospirosis is a worldwide zoonosis caused by spirochetes from the genus Leptospira. Pathogenic leptospires are able to escape from complement activation by binding to host complement inhibitors Factor H [FH] and C4b-binding protein (C4BP) while non-pathogenic leptospires are rapidly killed in the presence of fresh serum. In this study, we demonstrate that complement control protein domains (CCP) 7 and 8 of C4BP α-chain interact with the outer membrane proteins LcpA, LigA and LigB from the... (More)
- The complement system consists of more than 40 proteins that participate in the inflammatory response and in pathogen killing. Complement inhibitors are necessary to avoid the excessive consumption and activation of this system on host cells. Leptospirosis is a worldwide zoonosis caused by spirochetes from the genus Leptospira. Pathogenic leptospires are able to escape from complement activation by binding to host complement inhibitors Factor H [FH] and C4b-binding protein (C4BP) while non-pathogenic leptospires are rapidly killed in the presence of fresh serum. In this study, we demonstrate that complement control protein domains (CCP) 7 and 8 of C4BP α-chain interact with the outer membrane proteins LcpA, LigA and LigB from the pathogenic leptospire L. interrogans. The interaction between C4BP and LcpA, LigA and LigB is sensitive to ionic strength and inhibited by heparin. We fine mapped the LigA and LigB domains involved in its binding to C4BP and heparin and found that both interactions are mediated through the bacterial immunoglobulin-like (Big) domains 7 and 8 (LigA7-8 and LigB7-8) of both LigA and LigB and also through LigB9-10. Therefore, C4BP and heparin may share the same binding sites on Lig proteins. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/8147735
- author
- Breda, Leandro C D
; Hsieh, Ching-Lin
; Castiblanco Valencia, Mónica M
; da Silva, Ludmila B
; Barbosa, Angela S
; Blom, Anna
LU
; Yung-Fu, Chang
and Isaac, Lourdes
- organization
- publishing date
- 2015
- type
- Contribution to journal
- publication status
- published
- subject
- in
- PLoS Neglected Tropical Diseases
- volume
- 9
- issue
- 10
- article number
- e0004192
- publisher
- Public Library of Science (PLoS)
- external identifiers
-
- pmid:26517116
- wos:000364459600077
- scopus:84949906868
- ISSN
- 1935-2735
- DOI
- 10.1371/journal.pntd.0004192
- language
- English
- LU publication?
- yes
- id
- 890d7236-777e-4dce-871a-9178035c14dd (old id 8147735)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/26517116?dopt=Abstract
- date added to LUP
- 2016-04-01 09:55:34
- date last changed
- 2022-05-05 08:58:14
@article{890d7236-777e-4dce-871a-9178035c14dd,
abstract = {{The complement system consists of more than 40 proteins that participate in the inflammatory response and in pathogen killing. Complement inhibitors are necessary to avoid the excessive consumption and activation of this system on host cells. Leptospirosis is a worldwide zoonosis caused by spirochetes from the genus Leptospira. Pathogenic leptospires are able to escape from complement activation by binding to host complement inhibitors Factor H [FH] and C4b-binding protein (C4BP) while non-pathogenic leptospires are rapidly killed in the presence of fresh serum. In this study, we demonstrate that complement control protein domains (CCP) 7 and 8 of C4BP α-chain interact with the outer membrane proteins LcpA, LigA and LigB from the pathogenic leptospire L. interrogans. The interaction between C4BP and LcpA, LigA and LigB is sensitive to ionic strength and inhibited by heparin. We fine mapped the LigA and LigB domains involved in its binding to C4BP and heparin and found that both interactions are mediated through the bacterial immunoglobulin-like (Big) domains 7 and 8 (LigA7-8 and LigB7-8) of both LigA and LigB and also through LigB9-10. Therefore, C4BP and heparin may share the same binding sites on Lig proteins.}},
author = {{Breda, Leandro C D and Hsieh, Ching-Lin and Castiblanco Valencia, Mónica M and da Silva, Ludmila B and Barbosa, Angela S and Blom, Anna and Yung-Fu, Chang and Isaac, Lourdes}},
issn = {{1935-2735}},
language = {{eng}},
number = {{10}},
publisher = {{Public Library of Science (PLoS)}},
series = {{PLoS Neglected Tropical Diseases}},
title = {{Fine Mapping of the Interaction between C4b-Binding Protein and Outer Membrane Proteins LigA and LigB of Pathogenic Leptospira interrogans.}},
url = {{https://lup.lub.lu.se/search/files/1391057/8839740.PDF}},
doi = {{10.1371/journal.pntd.0004192}},
volume = {{9}},
year = {{2015}},
}