Binding characteristics of thrombin-activatable fibrinolysis inhibitor to streptococcal surface collagen-like proteins A and B
(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:
https://lup.lub.lu.se/record/2208108
- author
- Seron, Mercedes Valls ; Plug, Tom ; Marquart, J. Arnoud ; Marx, Pauline F. ; Herwald, Heiko LU ; de Groot, Philip G. and Meijers, Joost C. M.
- organization
- publishing date
- 2011
- 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}}, }