Interaction between the variant form of fibrinogen and factor XIII: potential role of sulfotyrosine residues

M. Moaddel, David Farrell

Research output: Contribution to journalArticle

Abstract

Fibrinogen, (0β7)2, is cleaved by thrombin to generate fibrin, the end product of the blood coagulation cascade. Fibrin clots are cross-linked by factor XIII, a transglutaminase that forms a covalent bond between lysine and glutamine side chains, thereby making the clot more resistant to fibrinolysis. A minor variant form of fibrinogen, denoted 7,1/7' fibrinogen, contains a twenty amino acid sequence that is substituted for the last four carboxy terminal amino acids and includes two tyrosine residues that are sulfated. 7,4/7' fibrinogen acts as a carrier protein for factor XIII. We have tested the hypothesis that the binding interaction between 7x/7' fibrinogen and factor XIII occurs via these sulfotyrosyl residues by generating recombinant homodimeric fibrinogen. Biosynthetic labeling of transfected baby hamster kidney cells expressing recombinant IA/IA Fbg, T'/7' Fbg, 7'Y418F/7'Y418F Fbg, 7'Y422F/7'Y422F Fbg and 7'Y418FY422F/7'Y418F-Y422F Fbg demonstrated that Tyr422 is incompletely sulfated. This result is consistent with the observation that Tyr418 follows Huttner's consensus sequence whereas Tyr422 does not. Sedimentation equilibrium studies suggest that sulfation is not essential for the 7,4/7' fibrinogen/factor XIII interaction to occur. The recombinant 7'Y418F-Y422F/7'Y418F-Y422F Fbg forms a detectable complex with factor XIII as seen for r7'/7' Fbg and factor XIII. Although tyrosine sulfation may not be absolutely necessary for 7/1/7' fibrinogen/factor XIII complex formation, it may affect the strength of the interaction.

Original languageEnglish (US)
JournalFASEB Journal
Volume12
Issue number8
StatePublished - 1998
Externally publishedYes

Fingerprint

Factor XIII
fibrinogen
Fibrinogen
fibrin
Fibrin
Tyrosine
tyrosine
fibrinolysis
Amino Acids
blood coagulation
Transglutaminases
Covalent bonds
thrombin
tyrosine O-sulfate
protein-glutamine gamma-glutamyltransferase
consensus sequence
Consensus Sequence
transport proteins
Blood Coagulation
Fibrinolysis

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

Cite this

Interaction between the variant form of fibrinogen and factor XIII : potential role of sulfotyrosine residues. / Moaddel, M.; Farrell, David.

In: FASEB Journal, Vol. 12, No. 8, 1998.

Research output: Contribution to journalArticle

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