Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

Binding characteristics of thrombin-activatable fibrinolysis inhibitor to streptococcal surface collagen-like proteins A and B

Seron, Mercedes Valls ; Plug, Tom ; Marquart, J. Arnoud ; Marx, Pauline F. ; Herwald, Heiko LU orcid ; de Groot, Philip G. and Meijers, Joost C. M. (2011) In Thrombosis and Haemostasis 106(4). p.609-616
Abstract
Streptococcus pyogenes is the causative agent in a wide range of diseases in humans. Thrombin-activatable fibrinolysis inhibitor (TAFI) binds to collagen-like proteins ScIA and ScIB at the surface of S. pyogenes. Activation of TAFI at this surface redirects inflammation from a transient to chronic state by modulation of the kallikrein/kinin system. We investigated TAFI binding characteristics to ScIA/ScIB. Thirty-four overlapping TAFI peptides of 20 amino acids were generated. Two of these peptides (P18: residues G205-S221, and P19: R214-0232) specifically bound to ScIA/ScIB with high affinity, and competed in a dose-dependent manner with TAFI binding to ScIA/ScIB. In another series of experiments, the binding properties of activated TAFI... (More)
Streptococcus pyogenes is the causative agent in a wide range of diseases in humans. Thrombin-activatable fibrinolysis inhibitor (TAFI) binds to collagen-like proteins ScIA and ScIB at the surface of S. pyogenes. Activation of TAFI at this surface redirects inflammation from a transient to chronic state by modulation of the kallikrein/kinin system. We investigated TAFI binding characteristics to ScIA/ScIB. Thirty-four overlapping TAFI peptides of 20 amino acids were generated. Two of these peptides (P18: residues G205-S221, and P19: R214-0232) specifically bound to ScIA/ScIB with high affinity, and competed in a dose-dependent manner with TAFI binding to ScIA/ScIB. In another series of experiments, the binding properties of activated TAFI (TAFIa) to ScIA/ScIB were studied with a quadruple TAF1 mutant (TAFI-IIYQ) that after activation is a 70-fold more stable enzyme than wild-type TAFIa. TAFI and TAFI-IIYQ bound to the bacterial proteins with similar affinities. The rate of dissociation was different between the proenzyme (both TAF1 and TAFI-IIYQ) and the stable enzyme TAFIa-IIYQ. TAFIa-IIYQ bound to ScIA/ScIB, but dissociated faster than TAFI-IIYQ. In conclusion, the bacterial proteins ScIA and ScIB bind to a TAR fragment encompassing residues G205-D232. Binding of TAFI to the bacteria may allow activation of TAR, whereafter the enzyme easily dissociates. (Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
TAFI, collagen-like proteins, protein binding, Streptococcus pyogenes
in
Thrombosis and Haemostasis
volume
106
issue
4
pages
609 - 616
publisher
Schattauer GmbH
external identifiers
  • wos:000296030500007
  • scopus:80053203134
  • pmid:21800008
ISSN
0340-6245
DOI
10.1160/TH11-03-0204
language
English
LU publication?
yes
id
4a413d2d-cca9-44cd-9d22-1d1594c129cd (old id 2208108)
date added to LUP
2016-04-01 14:33:36
date last changed
2022-04-14 18:28:23
@article{4a413d2d-cca9-44cd-9d22-1d1594c129cd,
  abstract     = {{Streptococcus pyogenes is the causative agent in a wide range of diseases in humans. Thrombin-activatable fibrinolysis inhibitor (TAFI) binds to collagen-like proteins ScIA and ScIB at the surface of S. pyogenes. Activation of TAFI at this surface redirects inflammation from a transient to chronic state by modulation of the kallikrein/kinin system. We investigated TAFI binding characteristics to ScIA/ScIB. Thirty-four overlapping TAFI peptides of 20 amino acids were generated. Two of these peptides (P18: residues G205-S221, and P19: R214-0232) specifically bound to ScIA/ScIB with high affinity, and competed in a dose-dependent manner with TAFI binding to ScIA/ScIB. In another series of experiments, the binding properties of activated TAFI (TAFIa) to ScIA/ScIB were studied with a quadruple TAF1 mutant (TAFI-IIYQ) that after activation is a 70-fold more stable enzyme than wild-type TAFIa. TAFI and TAFI-IIYQ bound to the bacterial proteins with similar affinities. The rate of dissociation was different between the proenzyme (both TAF1 and TAFI-IIYQ) and the stable enzyme TAFIa-IIYQ. TAFIa-IIYQ bound to ScIA/ScIB, but dissociated faster than TAFI-IIYQ. In conclusion, the bacterial proteins ScIA and ScIB bind to a TAR fragment encompassing residues G205-D232. Binding of TAFI to the bacteria may allow activation of TAR, whereafter the enzyme easily dissociates.}},
  author       = {{Seron, Mercedes Valls and Plug, Tom and Marquart, J. Arnoud and Marx, Pauline F. and Herwald, Heiko and de Groot, Philip G. and Meijers, Joost C. M.}},
  issn         = {{0340-6245}},
  keywords     = {{TAFI; collagen-like proteins; protein binding; Streptococcus pyogenes}},
  language     = {{eng}},
  number       = {{4}},
  pages        = {{609--616}},
  publisher    = {{Schattauer GmbH}},
  series       = {{Thrombosis and Haemostasis}},
  title        = {{Binding characteristics of thrombin-activatable fibrinolysis inhibitor to streptococcal surface collagen-like proteins A and B}},
  url          = {{https://lup.lub.lu.se/search/files/4037453/2294062.pdf}},
  doi          = {{10.1160/TH11-03-0204}},
  volume       = {{106}},
  year         = {{2011}},
}