Interactions of human fibrinogens with factor XIII: Roles of calcium and the γ' peptide

Maia Moaddel, David Farrell, Margaret A. Daugherty, Michael G. Fried

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Plasma factor XIII is the zymogen of the transglutaminase factor XIIIa. This enzyme catalyzes the formation of isopeptide cross-links between fibrin molecules in nascent blood clots that greatly increase the mechanical stability of clots and their resistance to thrombolytic enzymes. We have characterized the solution interactions of factor XIII with two variants of fibrinogen, the soluble precursor of fibrin. Both the predominant fibrinogen γ(A)/γ(A) and the major variant γ(A)/γ' form complexes with a 2 fibrinogen:1 factor XIII ratio. The absence of detectable concentrations of 1:1 complexes in equilibrium mixtures containing free factor XIII and 2:1 complexes suggests that this interaction is cooperative. Factor XIII binds fibrinogen γ(A)/γ' ~20-fold more tightly than fibrinogen γ(A)/γ(A), and the interaction with fibrinogen γ(A)/γ' (but not fibrinogen γ(A)/γ(A) is accompanied by a significant release of Ca2+. Taken together, these results suggest that the strikingly anionic γ' C-terminal sequence contains features that are important for factor XIII binding. Consistent with this notion, a synthetic 20-residue polypeptide containing the γ' sequence was found to associate with factor XIII in a 2:1 molar ratio and act as an efficient competitor for fibrinogen γ(A)/γ' binding.

Original languageEnglish (US)
Pages (from-to)6698-6705
Number of pages8
JournalBiochemistry
Volume39
Issue number22
DOIs
StatePublished - Jun 6 2000

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Factor XIII
Fibrinogen
Calcium
Peptides
Fibrin
Factor XIIIa
Enzyme Precursors
Transglutaminases
Mechanical stability
Enzymes
Thrombosis
Blood
Plasmas
Molecules

ASJC Scopus subject areas

  • Biochemistry

Cite this

Interactions of human fibrinogens with factor XIII : Roles of calcium and the γ' peptide. / Moaddel, Maia; Farrell, David; Daugherty, Margaret A.; Fried, Michael G.

In: Biochemistry, Vol. 39, No. 22, 06.06.2000, p. 6698-6705.

Research output: Contribution to journalArticle

Moaddel, Maia ; Farrell, David ; Daugherty, Margaret A. ; Fried, Michael G. / Interactions of human fibrinogens with factor XIII : Roles of calcium and the γ' peptide. In: Biochemistry. 2000 ; Vol. 39, No. 22. pp. 6698-6705.
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