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

Mercedes Valls Serón; Tom Plug; J. Arnoud Marquart; Pauline F. Marx; Heiko Herwald; Philip G. de Groot; Joost C. M. Meijers

doi:10.1160/TH11-03-0204

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2011; 106(04): 609-616
DOI: 10.1160/TH11-03-0204

Blood Coagulation, Fibrinolysis and Cellular Haemostasis

Schattauer GmbH

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

Mercedes Valls Serón

¹Experimental Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands

³Clinical Chemistry and Haematology, University Medical Center, Utrecht University, Utrecht, the Netherlands

,

Tom Plug

¹Experimental Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands

,

J. Arnoud Marquart

¹Experimental Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands

,

Pauline F. Marx

¹Experimental Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands

,

Heiko Herwald

²Department of Clinical Sciences, Section for Clinical and Experimental Infection Medicine, Lund University

,

Philip G. de Groot

³Clinical Chemistry and Haematology, University Medical Center, Utrecht University, Utrecht, the Netherlands

,

Joost C. M. Meijers

¹Experimental Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands

› Author Affiliations

Abstract

Summary

Streptococcus pyogenes is the causative agent in a wide range of diseases in humans. Thrombin-activatable fibrinolysis inhibitor (TAFI) binds to collagen-like proteins SclA and SclB 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 SclA/SclB. Thirty-four overlapping TAFI peptides of ∼20 amino acids were generated. Two of these peptides (P18: residues G205-S221, and P19: R214-D232) specifically bound to SclA/SclB with high affinity, and competed in a dose-dependent manner with TAFI binding to SclA/SclB. In another series of experiments, the binding properties of activated TAFI (TAFIa) to SclA/SclB were studied with a quadruple TAFI 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 TAFI and TAFI-IIYQ) and the stable enzyme TAFIa-IIYQ. TAFIa-IIYQ bound to SclA/ SclB, but dissociated faster than TAFI-IIYQ. In conclusion, the bacterial proteins SclA and SclB bind to a TAFI fragment encompassing residues G205-D232. Binding of TAFI to the bacteria may allow activation of TAFI, whereafter the enzyme easily dissociates.

Keywords

TAFI - collagen-like proteins - protein binding - Streptococcus pyogenes

Full Text

References

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