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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:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
PLoS Neglected Tropical Diseases
volume
9
issue
10
publisher
Public Library of Science
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
2015-11-04 21:19:36
date last changed
2017-07-30 03:02:53
@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.},
  articleno    = {e0004192},
  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},
  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          = {http://dx.doi.org/10.1371/journal.pntd.0004192},
  volume       = {9},
  year         = {2015},
}