Exploring the structural similarity yet functional distinction between coagulation factor XIII-B and complement factor H sushi domains
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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.
KeywordsFactor XIII Factor XIIIb Complement system proteins Complement factor h
AB and JO are the principle investigators of the study. MSA and SS performed the laboratory experiments. MSA, SS and AB analyzed the data, generated the images and co-wrote the article. AB, HY, VI and JO edited and revised the article. AB designed the study. None of the authors have any conflict of interest in the following work. The authors would like to acknowledge technical help from Sophie Lyonga.
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Conflict of interest
Authors declare no conflict of interest.
This article does not contain any studies with animals performed by any of the authors.
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