| Factor XIII: novel structural and functional aspects. | |
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MedLine Citation:
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PMID: 20880254 Owner: NLM Status: In-Process |
Abstract/OtherAbstract:
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Factor (F)XIII is a protransglutaminase that, in addition to maintaining hemostasis, has multiple plasmatic and intracellular functions. Its plasmatic form (pFXIII) is a tetramer of two potentially active A (FXIII-A) and two inhibitory/carrier B (FXIII-B) subunits, whereas its cellular form (cFXIII) is a dimer of FXIII-A. FXIII-A belongs to the family of transglutaminases (TGs), which show modest similarity in the primary structure, but a high degree of conservatism in their domain and sub-domain secondary structure. FXIII-A consists of an activation peptide, a β-sandwich, a catalytic and two β-barrel domains. FXIII-B is a glycoprotein consisting of 10 repetitive sushi domains each held together by two internal disulfide bonds. The structural elements of FXIII-A involved in the interaction with FXIII-B have not been elucidated; in FXIII-B the first sushi domain seems important for complex formation. In the circulation pFXIII is bound to the fibrinogen γ'-chain through its B subunit. In the process of pFXIII activation first thrombin cleaves off the activation peptide from FXIII-A, then in the presence of Ca(2+) FXIII-B dissociates and FXIII-A becomes transformed into an active transglutaminase (FXIIIa). The activation is highly accelerated by the presence of fibrin(ogen). cFXIII does not require proteolysis for intracellular activation. The three-dimensional structure of FXIIIa has not been resolved. Based on analogies with transglutaminase-2, a three-dimensional structure of FXIIIa was developed by molecular modeling, which shows good agreement with the drastic structural changes demonstrated by biochemical studies. The structural requirements for enzyme-substrate interaction and for transglutaminase activity are also reviewed. |
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Authors:
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I Komáromi; Z Bagoly; L Muszbek |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of thrombosis and haemostasis : JTH Volume: 9 ISSN: 1538-7836 ISO Abbreviation: J. Thromb. Haemost. Publication Date: 2011 Jan |
Date Detail:
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Created Date: 2011-01-07 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101170508 Medline TA: J Thromb Haemost Country: England |
Other Details:
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Languages: eng Pagination: 9-20 Citation Subset: IM |
Copyright Information:
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© 2010 International Society on Thrombosis and Haemostasis. |
Affiliation:
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Clinical Research Center Thrombosis, Haemostasis and Vascular Biology Research Group of the Hungarian Academy of Sciences, University of Debrecen, Medical and Health Science Center, Debrecen, Hungary. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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