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

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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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References

  1. Amara U, Flierl MA, Rittirsch D et al (2010) Molecular intercommunication between the complement and coagulation systems. J Immunol 185(9):5628–5636. https://doi.org/10.4049/jimmunol.0903678

    Article  CAS  PubMed  Google Scholar 

  2. Esmon CT (2004) The impact of the inflammatory response on coagulation. Thromb Res 114(5–6):321–327. https://doi.org/10.1016/j.thromres.2004.06.028

    Article  CAS  PubMed  Google Scholar 

  3. Krisinger MJ, Goebeler V, Lu Z et al (2012) Thrombin generates previously unidentified C5 products that support the terminal complement activation pathway. Blood 120(8):1717–1725. https://doi.org/10.1182/blood-2012-02-412080

    Article  CAS  PubMed  Google Scholar 

  4. Foley JH, Walton BL, Aleman MM et al (2016) Complement activation in arterial and venous thrombosis is mediated by plasmin. EBioMedicine 5:175–182. https://doi.org/10.1016/j.ebiom.2016.02.011

    Article  PubMed  PubMed Central  Google Scholar 

  5. Markiewski MM, DeAngelis RA, Lambris JD (2008) Complexity of complement activation in sepsis. J Cell Mol Med 12(6a):2245–2254. https://doi.org/10.1111/j.1582-4934.2008.00504.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Jenny L, Dobó J, Gál P et al (2018) MASP-1 of the complement system enhances clot formation in a microvascular whole blood flow model. PLoS ONE 13(1):e0191292. https://doi.org/10.1371/journal.pone.0191292

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Adamiak M, Abdelbaset-Ismail A, Suszynska M et al (2017) Novel evidence that the mannan-binding lectin pathway of complement activation plays a pivotal role in triggering mobilization of hematopoietic stem/progenitor cells by activation of both the complement and coagulation cascades. Leukemia 31(1):262–265. https://doi.org/10.1038/leu.2016.278

    Article  CAS  PubMed  Google Scholar 

  8. Gupta S, Biswas A, Akhter MS et al (2016) Revisiting the mechanism of coagulation factor XIII activation and regulation from a structure/functional perspective. Sci Rep 6(1):245. https://doi.org/10.1038/srep30105

    Article  CAS  Google Scholar 

  9. Biswas A, Thomas A, Bevans CG et al (2013) In vitro secretion deficits are common among human coagulation factor XIII subunit B missense mutants. Correlations with patient phenotypes and molecular models. Human Mutation 34(11):1490–1500. https://doi.org/10.1002/humu.22391

    Article  CAS  PubMed  Google Scholar 

  10. Thomas A, Biswas A, Ivaskevicius V et al (2015) Structural and functional influences of coagulation factor XIII subunit B heterozygous missense mutants. Mol Genet Genomic Med 3(4):258–271. https://doi.org/10.1002/mgg3.138

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Schroeder V, Kohler H (2016) Factor XIII: structure and function. Semin Thromb Hemost 42(04):422–428. https://doi.org/10.1055/s-0036-1571341

    Article  CAS  PubMed  Google Scholar 

  12. Souri M, Kaetsu H, Ichinose A (2008) Sushi domains in the B subunit of factor XIII responsible for oligomer assembly. Biochemistry 47(33):8656–8664. https://doi.org/10.1021/bi8006143

    Article  CAS  PubMed  Google Scholar 

  13. Mezei ZA, Katona É, Kállai J et al (2017) Factor XIII levels and factor XIII B subunit polymorphisms in patients with venous thromboembolism. Thromb Res 158:93–97. https://doi.org/10.1016/j.thromres.2017.08.018

    Article  CAS  PubMed  Google Scholar 

  14. Pitkänen HH, Jouppila A, Lemponen M et al (2017) Factor XIII deficiency enhances thrombin generation due to impaired fibrin polymerization - An effect corrected by Factor XIII replacement. Thromb Res 149:56–61. https://doi.org/10.1016/j.thromres.2016.11.012

    Article  CAS  PubMed  Google Scholar 

  15. Deicke C, Chakrakodi B, Pils MC et al (2016) Local activation of coagulation factor XIII reduces systemic complications and improves the survival of mice after Streptococcus pyogenes M1 skin infection. Int J Med Microbiol 306(7):572–579. https://doi.org/10.1016/j.ijmm.2016.06.001

    Article  CAS  PubMed  Google Scholar 

  16. Orosz ZZ, Katona É, Facskó A et al (2011) Factor XIII subunits in human tears; their highly elevated levels following penetrating keratoplasty. Clin Chim Acta 412(3–4):271–276. https://doi.org/10.1016/j.cca.2010.10.017

    Article  CAS  PubMed  Google Scholar 

  17. Ariëns RA, Kohler HP, Mansfield MW et al (1999) Subunit antigen and activity levels of blood coagulation factor XIII in healthy individuals. Relation to sex, age, smoking, and hypertension. Arterioscl Thromb Vasc Biol 19(8):2012–2016

    Article  PubMed  Google Scholar 

  18. Kopp A, Hebecker M, Svobodova E et al (2012) Factor H. A complement regulator in health and disease, and a mediator of cellular interactions. Biomolecules 2(1):46–75. https://doi.org/10.3390/biom2010046

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Rodriguez de Cordoba S, Rey-Campos J, Dykes DD et al (1988) Coagulation factor XIII B subunit is encoded by a gene linked to the regulator of complement activation (RCA) gene cluster in man. Immunogenetics 28(6):452–454

    Article  Google Scholar 

  20. Fagerberg L, Hallström BM, Oksvold P et al (2014) Analysis of the human tissue-specific expression by genome-wide integration of transcriptomics and antibody-based proteomics. Mol Cell Prot 13(2):397–406. https://doi.org/10.1074/mcp.M113.035600

    Article  CAS  Google Scholar 

  21. Simon Á, Bagoly Z, Hevessy Z et al (2012) Expression of coagulation factor XIII subunit A in acute promyelocytic leukemia. Cytometry 82B(4):209–216. https://doi.org/10.1002/cyto.b.21019

    Article  CAS  Google Scholar 

  22. Thomas A, Gasque P, Vaudry D et al (2000) Expression of a complete and functional complement system by human neuronal cells in vitro. Int Immunol 12(7):1015–1023

    Article  CAS  PubMed  Google Scholar 

  23. Okemefuna AI, Nan R, Gor J et al (2009) Electrostatic Interactions Contribute to the Folded-back Conformation of Wild Type Human Factor H. J Mol Biol 391(1):98–118. https://doi.org/10.1016/j.jmb.2009.06.010

    Article  CAS  PubMed  Google Scholar 

  24. Aslam M, Perkins SJ (2001) Folded-back solution structure of monomeric factor H of human complement by synchrotron X-ray and neutron scattering, analytical ultracentrifugation and constrained molecular modelling. J Mol Biol 309(5):1117–1138. https://doi.org/10.1006/jmbi.2001.4720

    Article  CAS  PubMed  Google Scholar 

  25. Moore BL, Kelley LA, Barber J et al (2013) High-quality protein backbone reconstruction from alpha carbons using Gaussian mixture models. J Comput Chem 34(22):1881–1889. https://doi.org/10.1002/jcc.23330

    Article  CAS  PubMed  Google Scholar 

  26. Xu D, Jaroszewski L, Li Z et al (2014) AIDA: ab initio domain assembly server. Nucleic Acids Res 42(W1):W308–W313. https://doi.org/10.1093/nar/gku369

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Krieger E, Koraimann G, Vriend G (2002) Increasing the precision of comparative models with YASARA NOVA—a self-parameterizing force field. Proteins 47(3):393–402

    Article  CAS  PubMed  Google Scholar 

  28. Krieger E, Vriend G (2014) YASARA View: molecular graphics for all devices—from smartphones to workstations. Bioinformatics 30(20):2981–2982. https://doi.org/10.1093/bioinformatics/btu426

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Katona E, Haramura G, Kárpáti L et al (2000) A simple, quick one-step ELISA assay for the determination of complex plasma factor XIII (A2B2). Thromb Haemost 83(2):268–273

    Article  CAS  PubMed  Google Scholar 

  30. Katona EE, Ajzner E, Toth K et al (2001) Enzyme-linked immunosorbent assay for the determination of blood coagulation factor XIII A-subunit in plasma and in cell lysates. J Immunol Methods 258(1–2):127–135

    Article  CAS  Google Scholar 

  31. Lee KN, Birckbichler PJ, Patterson MK, JR (1988) Colorimetric assay of blood coagulation factor XIII in plasma. Clin Chem 34(5):906–910

    CAS  PubMed  Google Scholar 

  32. Krushkal J, Bat O, Gigli I (2000) Evolutionary relationships among proteins encoded by the regulator of complement activation gene cluster. Mol Biol Evol 17(11):1718–1730. https://doi.org/10.1093/oxfordjournals.molbev.a026270

    Article  CAS  PubMed  Google Scholar 

  33. Reid KBM, Bentley DR, Campbell RD et al (1986) Complement system proteins which interact with C3b or C4b A superfamily of structurally related proteins. Immunol Today 7(7–8):230–234. https://doi.org/10.1016/0167-5699(86)90110-6

    Article  CAS  PubMed  Google Scholar 

  34. Müller-Calleja N, Ritter S, Hollerbach A et al (2018) Complement C5 but not C3 is expendable for tissue factor activation by cofactor-independent antiphospholipid antibodies. Blood Adv 2(9):979–986. https://doi.org/10.1182/bloodadvances.2018017095

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Skjeflo EW, Christiansen D, Fure H et al (2018) Staphylococcus aureus-induced complement activation promotes tissue factor-mediated coagulation. J Thromb Haemost 16(5):905–918. https://doi.org/10.1111/jth.13979

    Article  CAS  PubMed  Google Scholar 

  36. Subramaniam S, Jurk K, Hobohm L et al (2017) Distinct contributions of complement factors to platelet activation and fibrin formation in venous thrombus development. Blood 129(16):2291–2302. https://doi.org/10.1182/blood-2016-11-749879

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Scheetz TE, Fingert JH, Wang K et al (2013) A genome-wide association study for primary open angle glaucoma and macular degeneration reveals novel loci. PLoS ONE 8(3):e58657. https://doi.org/10.1371/journal.pone.0058657

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Hageman GS, Gehrs K, Lejnine S et al (2011) Clinical validation of a genetic model to estimate the risk of developing choroidal neovascular age-related macular degeneration. Human Genom 5(5):420–440

    Article  CAS  Google Scholar 

  39. Schwartz ML, Pizzo SV, Hill RL et al (1973) Human Factor XIII from plasma and platelets. Molecular weights, subunit structures, proteolytic activation, and cross-linking of fibrinogen and fibrin. J Biol Chem 248(4):1395–1407

    CAS  PubMed  Google Scholar 

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Author notes

  1. Mohammad Suhail Akhter and Sneha Singh have contributed equally.

Authors and Affiliations

  1. Institute of Experimental Haematology and Transfusion Medicine, University Clinic Bonn, Sigmund Freud Str. 25, 53127, Bonn, Germany

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

  2. College of Applied Medical Sciences, Jazan University, Jazan, Saudi Arabia

    Mohammad Suhail Akhter

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Contributions

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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Correspondence to Arijit Biswas.

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Akhter, M.S., Singh, S., Yadegari, H. et al. Exploring the structural similarity yet functional distinction between coagulation factor XIII-B and complement factor H sushi domains. J Thromb Thrombolysis 48, 95–102 (2019). https://doi.org/10.1007/s11239-019-01841-w

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