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

作者：Seron Mercedes Valls; Plug Tom; Marquart J Arnoud; Marx Pauline F; Herwald Heiko; de Groot Philip G; Meijers Joost C M^*

来源：Thrombosis and Haemostasis, 2011, 106(4): 609-616.

DOI：10.1160/TH11-03-0204

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

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.

• 出版日期2011-10