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Published in:

01-07-2019

Exploring the structural similarity yet functional distinction between coagulation factor XIII-B and complement factor H sushi domains

Authors: Mohammad Suhail Akhter, Sneha Singh, Hamideh Yadegari, Vytautas Ivaskevicius, Johannes Oldenburg, Arijit Biswas

Published in: Journal of Thrombosis and Thrombolysis | Issue 1/2019

Abstract

Coagulation factor XIII (FXIII) covalently crosslinks pre-formed fibrin clots preventing their premature fibrinolysis. In plasma, FXIII circulates as a zymogenic heterotetramer composed of catalytic FXIII-A subunits, and carrier/regulatory FXIII-B subunits. FXIII-A is a well characterized component of this complex, and has been associated with several pleiotropic roles outside coagulation as well. In comparison only protective/regulatory roles towards the FXIII-A subunit have been identified for FXIII-B. Strong homology between FXIII-B and complement regulator Complement factor H suggests a putative role of FXIII-B in complement activation. In the current study we have analyzed the similarities and yet functional divergence of these two proteins using in silico sequence alignment and structural analysis. We have evaluated complement activation post reconstitution of FXIII components into FXIII deficient and CFH deficient plasma. We have also transiently expressed FXIII-B in SH-SY5Y cell lines and evaluated its effect on the endogenous complement activation. Our investigations show no effect of FXIII-B subunit on the rate of complement activation. Therefore we conclude that at a physiological level, FXIII-B subunit plays no role in the complement system, although a vestigial function in altered pathological states might still exist.

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Title: Exploring the structural similarity yet functional distinction between coagulation factor XIII-B and complement factor H sushi domains
Authors: Mohammad Suhail Akhter
Sneha Singh
Hamideh Yadegari
Vytautas Ivaskevicius
Johannes Oldenburg
Arijit Biswas
Publication date: 01-07-2019
Publisher: Springer US
Published in: Journal of Thrombosis and Thrombolysis / Issue 1/2019
Print ISSN: 0929-5305
Electronic ISSN: 1573-742X
DOI: https://doi.org/10.1007/s11239-019-01841-w

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