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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 ; 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
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
F K Schattauer Verlag Gmbh
external identifiers
  • wos:000296030500007
  • scopus:80053203134
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
2011-11-30 09:14:19
date last changed
2017-03-26 04:02:15
@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},
  keyword      = {TAFI,collagen-like proteins,protein binding,Streptococcus pyogenes},
  language     = {eng},
  number       = {4},
  pages        = {609--616},
  publisher    = {F K Schattauer Verlag Gmbh},
  series       = {Thrombosis and Haemostasis},
  title        = {Binding characteristics of thrombin-activatable fibrinolysis inhibitor to streptococcal surface collagen-like proteins A and B},
  url          = {http://dx.doi.org/10.1160/TH11-03-0204},
  volume       = {106},
  year         = {2011},
}