Cleavage of fibrin-derived D-dimer into monomers by endopeptidase from puff adder venom (Bitis arietans) acting at cross-linked sites of the .gamma.-chain. Sequence of carboxy-terminal cyanogen bromide .gamma.-chain fragments

Purves, Langley R.; Purves, Maud; Brandt, Wolf F.

doi:10.1021/bi00389a008

Cited by 42 publications

(38 citation statements)

References 13 publications

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“…Two of the major reactive Gln residues are found near the NH 2 -terminal of pro-CpU. The presence of closely spaced reactive Gln residues is quite common and has been shown in other proteins, including plasminogen activator inhibitor-2 (36), ␤ A3-crystallin (37), the ␥-chain of fibrinogen (38), and vitronectin (39). It is not possible to derive a consensus sequence for the amine acceptor sites in proteins, but it is common that reactive Gln residues are positioned near the NH 2 or COOH terminus (40).…”

Section: Discussionmentioning

confidence: 94%

Human Procarboxypeptidase U, or Thrombin-activable Fibrinolysis Inhibitor, Is a Substrate for Transglutaminases

Valnickova

Enghild

1998

Journal of Biological Chemistry

114

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Procarboxypeptidase U (EC 3.4.17.20) (pro-CpU), also known as plasma procarboxypeptidase B and thrombinactivable fibrinolysis inhibitor, is a human plasma protein that has been implicated in the regulation of fibrinolysis. In this study, we show that pro-CpU serves as a substrate for transglutaminases. Both factor XIIIa and tissue transglutaminase catalyzed the polymerization of pro-CpU and the cross-linking to fibrin as well as the incorporation of 5-dimethylaminonaphthalene-1-sulfonyl cadaverine (dansylcadaverine), [14 C]putrescine, and dansyl-PGGQQIV. These findings show that pro-CpU contains both amine acceptor (Gln) and amine donor (Lys) residues. The amine acceptor residues were identified as Gln 2 , Gln 5 , and Gln 292 , suggesting that both the activation peptide and the mature enzyme participate in the cross-linking reaction. These observations imply that transglutaminases may mediate covalent binding of pro-CpU to other proteins and cell surfaces in vivo. In particular, factor XIIIa may cross-link pro-CpU to fibrin during the latter part of the coagulation cascade, thereby helping protect the newly formed fibrin clot from premature plasmin degradation. Moreover, the cross-linking may facilitate the activation of pro-CpU, stabilize the enzymatic activity, and protect the active enzyme from further degradation.

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Section: Discussionmentioning

confidence: 94%

Human Procarboxypeptidase U, or Thrombin-activable Fibrinolysis Inhibitor, Is a Substrate for Transglutaminases

Valnickova

Enghild

1998

Journal of Biological Chemistry

114

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“…1). Since there is only one donor lysine residue at y-406 (25,26), we assume that trimeric and tetrameric crosslinked structures form by utilization of that same residue. Four bond arrangements can account for these structures (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…In the presence of plasma transglutaminase (factor XIIIa) and Ca2', fibrin molecules undergo covalent crosslinking by formation of E-(y-glutamyl)lysine [E-('y-Glu)Lys] isopeptide bonds (22,23). Intermolecular crosslinking between D domains forms dimers (24), which occur as reciprocal bridges between a lysine at position 406 of one 'y chain and a glutamine at position 398 or 399 of another (25)(26)(27)(28). In addition, slower intermolecular crosslinking among a chains creates oligomers and larger a-chain polymers (29)(30)(31).…”

mentioning

confidence: 99%

Identification of covalently linked trimeric and tetrameric D domains in crosslinked fibrin.

Mosesson

Siebenlist

Amrani

et al. 1989

Proc. Natl. Acad. Sci. U.S.A.

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Following proteolytic conversion of fibrinogen to fibrin, clot assembly commences with formation of double-stranded fibrils that subsequently branch extensively in forming a three-dimensional network. Plasmin digests of fibrin clots that had first been covalently crosslinked by plasma transglutaminase (factor XIIIa) contained multimeric proteolytic fragments composed of crosslinked outer (D) domains of neighboring fibrin molecules. Two of these were larger than the well-known "D dimer" fragment and corresponded to D trimers and D tetramers, respectively. Whereas D dimers originate from crosslinked D domains at bimolecular junctions within two-stranded fibrils, D trimers and D tetramers evidently arise through crosslinking of contiguous D domains at trimolecular and tetramolecular junctions or at fibril branch points, respectively. Measurement of the widths of fibrils comprising trifunctional branches in thin fiber networks revealed tetramolecular branch points, which are formed by bifurcation of two double-stranded fibrils. In addition, another type of trifunctional structure, which we term the trimolecular branch point, was composed of three double-stranded fibrils. Crosslinking of D domains to form trimers may occur at this type ofjunction. These findings add to our understanding of the crosslinking arrangements that stabilize fibrin clot structure and the ways that fibrin molecules polymerize to form branches in the clot matrix.Following proteolytic conversion of fibrinogen to fibrin, polymer assembly commences with formation of doublestranded fibrils in which fibrin molecules, by virtue of noncovalent intermolecular interactions between outer (D) and central (E) domains (1-6), are arranged in a staggered overlapping manner (7-13) (Fig. 1). Subsequently, lateral fibril associations result in increased fiber thickness (11,(16)(17)(18), which is believed to account for interfibril connections and the trifunctional branching structures that comprise the three-dimensional matrix (11,(18)(19)(20)(21). In the presence of plasma transglutaminase (factor XIIIa) and Ca2', fibrin molecules undergo covalent crosslinking by formation of E-(y-glutamyl)lysine [E-('y-Glu)Lys] isopeptide bonds (22,23). Intermolecular crosslinking between D domains forms dimers (24), which occur as reciprocal bridges between a lysine at position 406 of one 'y chain and a glutamine at position 398 or 399 of another (25)(26)(27)(28). In addition, slower intermolecular crosslinking among a chains creates oligomers and larger a-chain polymers (29-31).Plasmin digestion of crosslinked fibrin results in early release of crosslink-containing a-chain segments from core structures (32-36). Thus, their existence in fibrin does not contribute significantly to the structure of major intermediate or terminal plasmin core fragments. In contrast, the intermolecular e-(y-Glu)Lys y-chain bonds result in degradation products unique to crosslinked fibrin, of which the bimolecular fragment, "D dimer," is the most abundant and best characterized (32, 37-39...

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“…52,53 Cross-linking occurs within 5 to 10 minutes between Gln398 or 399 on the ␥-chain of one fibrin molecule and Lys406 on the ␥-chain of another, 52,54 resulting in the formation of 2 antiparallel isopeptide bonds that connect the D-regions of 2 fibrinogen molecules longitudinally.…”

Section: Substrates Of Factor Xiiia and Biological Consequences Of Crmentioning

confidence: 99%

Role of factor XIII in fibrin clot formation and effects of genetic polymorphisms

Ariëns

Lai

Weisel

et al. 2002

Blood

329

272

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Factor XIII and fibrinogen are unusual among clotting factors in that neither is a serine protease. Fibrin is the main protein constituent of the blood clot, which is stabilized by factor XIIIa through an amide or isopeptide bond that ligates adjacent fibrin monomers. Many of the structural and functional features of factor XIII and fibrin(ogen) have been elucidated by protein and gene analysis, site-directed mutagenesis, and x-ray crystallography. However, some of the molecular aspects involved in the complex processes of insoluble fibrin formation in vivo and in vitro remain unresolved. The findings of a relationship between fibrinogen, factor XIII, and cardiovascular or other thrombotic disorders have focused much attention on these 2 proteins. Of particular interest are associations between common variations in the genes of factor XIII and altered risk profiles for thrombosis. Although there is much debate regarding these observations, the implications for our understanding of clot formation and therapeutic intervention may be of major importance. In this review, we have summarized recent findings on the structure and function of factor XIII. This is followed by a review of the effects of genetic polymorphisms on protein structure/function and their relationship to disease. (Blood. 2002;100:743-754)

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Cleavage of fibrin-derived D-dimer into monomers by endopeptidase from puff adder venom (Bitis arietans) acting at cross-linked sites of the .gamma.-chain. Sequence of carboxy-terminal cyanogen bromide .gamma.-chain fragments

Cited by 42 publications

References 13 publications

Human Procarboxypeptidase U, or Thrombin-activable Fibrinolysis Inhibitor, Is a Substrate for Transglutaminases

Human Procarboxypeptidase U, or Thrombin-activable Fibrinolysis Inhibitor, Is a Substrate for Transglutaminases

Identification of covalently linked trimeric and tetrameric D domains in crosslinked fibrin.

Role of factor XIII in fibrin clot formation and effects of genetic polymorphisms

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