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Streptococcal beta protein has separate binding sites for human factor H and IgA-Fc.

Areschoug, Thomas LU ; Stålhammar-Carlemalm, Margaretha LU ; Karlsson, Ingrid LU and Lindahl, Gunnar LU (2002) In Journal of Biological Chemistry 277(15). p.12642-12648
Abstract
The group B streptococcus (GBS) is the most important cause of life-threatening bacterial infections in newborn infants. Protective immunity to GBS infection is elicited by several surface proteins, one of which, the beta protein, is known to bind human IgA-Fc. Here, we show that the beta protein also binds human factor H (FH), a negative regulator of complement activation. Absorption experiments with whole human plasma demonstrated binding of FH to a GBS strain expressing beta protein, but not to an isogenic beta-negative mutant. This binding was due to a direct interaction between beta and FH, as shown by experiments with purified proteins. Inhibition tests and studies with beta fragments demonstrated that FH and IgA-Fc bind to separate... (More)
The group B streptococcus (GBS) is the most important cause of life-threatening bacterial infections in newborn infants. Protective immunity to GBS infection is elicited by several surface proteins, one of which, the beta protein, is known to bind human IgA-Fc. Here, we show that the beta protein also binds human factor H (FH), a negative regulator of complement activation. Absorption experiments with whole human plasma demonstrated binding of FH to a GBS strain expressing beta protein, but not to an isogenic beta-negative mutant. This binding was due to a direct interaction between beta and FH, as shown by experiments with purified proteins. Inhibition tests and studies with beta fragments demonstrated that FH and IgA-Fc bind to separate and non-overlapping regions in beta. Heparin, a known ligand for FH, specifically inhibited the binding between beta and FH, suggesting that FH has overlapping binding sites for beta and heparin. Bacteria-bound FH retained its complement regulatory activity, implying that beta-expressing GBS may use bound FH to evade complement attack. The finding that beta protein binds FH adds to a growing list of interactions between human pathogens and complement regulatory proteins, supporting the notion that these interactions are of general importance in bacterial pathogenesis. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Binding Sites, Streptococcus/*metabolism, Non-U.S. Gov't, Support, Fc/blood/*metabolism, Antigens, CD/blood/*metabolism, Base Sequence, Bacterial Proteins/*metabolism, Receptors, Human, Complement Factor H/*metabolism, DNA Primers
in
Journal of Biological Chemistry
volume
277
issue
15
pages
12642 - 12648
publisher
ASBMB
external identifiers
  • wos:000175036300021
  • scopus:0037066750
ISSN
1083-351X
DOI
10.1074/jbc.M112072200
language
English
LU publication?
yes
id
2ea40d59-2c7d-479c-a426-0752df8cfacd (old id 106417)
alternative location
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11812795&dopt=Abstract
date added to LUP
2007-07-09 15:18:28
date last changed
2017-01-01 04:34:05
@article{2ea40d59-2c7d-479c-a426-0752df8cfacd,
  abstract     = {The group B streptococcus (GBS) is the most important cause of life-threatening bacterial infections in newborn infants. Protective immunity to GBS infection is elicited by several surface proteins, one of which, the beta protein, is known to bind human IgA-Fc. Here, we show that the beta protein also binds human factor H (FH), a negative regulator of complement activation. Absorption experiments with whole human plasma demonstrated binding of FH to a GBS strain expressing beta protein, but not to an isogenic beta-negative mutant. This binding was due to a direct interaction between beta and FH, as shown by experiments with purified proteins. Inhibition tests and studies with beta fragments demonstrated that FH and IgA-Fc bind to separate and non-overlapping regions in beta. Heparin, a known ligand for FH, specifically inhibited the binding between beta and FH, suggesting that FH has overlapping binding sites for beta and heparin. Bacteria-bound FH retained its complement regulatory activity, implying that beta-expressing GBS may use bound FH to evade complement attack. The finding that beta protein binds FH adds to a growing list of interactions between human pathogens and complement regulatory proteins, supporting the notion that these interactions are of general importance in bacterial pathogenesis.},
  author       = {Areschoug, Thomas and Stålhammar-Carlemalm, Margaretha and Karlsson, Ingrid and Lindahl, Gunnar},
  issn         = {1083-351X},
  keyword      = {Binding Sites,Streptococcus/*metabolism,Non-U.S. Gov't,Support,Fc/blood/*metabolism,Antigens,CD/blood/*metabolism,Base Sequence,Bacterial Proteins/*metabolism,Receptors,Human,Complement Factor H/*metabolism,DNA Primers},
  language     = {eng},
  number       = {15},
  pages        = {12642--12648},
  publisher    = {ASBMB},
  series       = {Journal of Biological Chemistry},
  title        = {Streptococcal beta protein has separate binding sites for human factor H and IgA-Fc.},
  url          = {http://dx.doi.org/10.1074/jbc.M112072200},
  volume       = {277},
  year         = {2002},
}