title: The Non-catalytic B Subunit of Coagulation Factor XIII Accelerates Fibrin Cross-linking.
abstract: Covalent cross-linking of fibrin chains is required for stable blood clot formation, which is catalyzed by coagulation factor XIII (FXIII), a proenzyme of plasma transglutaminase consisting of catalytic A (FXIII-A) and non-catalytic B subunits (FXIII-B). Herein, we demonstrate that FXIII-B accelerates fibrin cross-linking. Depletion of FXIII-B from normal plasma supplemented with a physiological level of recombinant FXIII-A resulted in delayed fibrin cross-linking, reduced incorporation of FXIII-A into fibrin clots, and impaired activation peptide cleavage by thrombin; the addition of recombinant FXIII-B restored normal fibrin cross-linking, FXIII-A incorporation into fibrin clots, and activation peptide cleavage by thrombin. Immunoprecipitation with an anti-fibrinogen antibody revealed an interaction between the FXIII heterotetramer and fibrinogen mediated by FXIII-B and not FXIII-A. FXIII-B probably binds the γ-chain of fibrinogen with its D-domain, which is near the fibrin polymerization pockets, and dissociates from fibrin during or after cross-linking between γ-chains. Thus, FXIII-B plays important roles in the formation of a ternary complex between proenzyme FXIII, prosubstrate fibrinogen, and activator thrombin. Accordingly, congenital or acquired FXIII-B deficiency may result in increased bleeding tendency through impaired fibrin stabilization due to decreased FXIII-A activation by thrombin and secondary FXIII-A deficiency arising from enhanced circulatory clearance.
authors: From the Department of Molecular Patho-Biochemistry and Patho-Biology, Yamagata University School of Medicine, 2-2-2 Iida-Nishi, Yamagata, 990-9585 Japan.
authors: Masayoshi
authors: M
authors: Souri
authors: From the Department of Molecular Patho-Biochemistry and Patho-Biology, Yamagata University School of Medicine, 2-2-2 Iida-Nishi, Yamagata, 990-9585 Japan.
authors: Tsukasa
authors: T
authors: Osaki
authors: From the Department of Molecular Patho-Biochemistry and Patho-Biology, Yamagata University School of Medicine, 2-2-2 Iida-Nishi, Yamagata, 990-9585 Japan aichinos@med.id.yamagata-u.ac.jp.
authors: Akitada
authors: A
authors: Ichinose
mesh_terms: D001777:Blood Coagulation; D020134:Catalytic Domain; D003029:Coagulants / Q000737:chemistry; D003432:Cross-Linking Reagents / Q000737:chemistry*; D018360:Crystallography, X-Ray; D005176:Factor XIII / Q000737:chemistry*; D005337:Fibrin / Q000737:chemistry*; D005340:Fibrinogen / Q000378:metabolism; D005341:Fibrinolysin / Q000737:chemistry; D006801:Humans; D010455:Peptides / Q000737:chemistry; D010641:Phenotype; D053719:Tandem Mass Spectrometry; D013917:Thrombin / Q000737:chemistry; D011503:Transglutaminases / Q000737:chemistry
chemical_list: D003029:Coagulants; D003432:Cross-Linking Reagents; D010455:Peptides; D005337:Fibrin; D005340:Fibrinogen; D005176:Factor XIII; D011503:Transglutaminases; D013917:Thrombin; D005341:Fibrinolysin
keywords: Bleeding Disease; Blood; Coagulation Factor; Fibrin; Protein Cross-linking; Transglutaminase