Characterization of factor xiii-γ/γ fibrinogen complexesd

H. Farrell, M. G. Fried, L. A. Falls

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Abstract

About 10% of human plasma fibrinogen is a heterodimer of the composition (a/J')(afl?). The two different 3' chains, 3' and 3', arise from alternative mRNA processing. The 7' chain contains a 20-amino acid extension at the C-terminus that replaces a 4-residue sequence in the 3' chain. Siebenlist, Meh. and Mosesson (Biochemistry 35:10448-10453 (1996)) have shown that the ' chain, but not the 3'A chain, binds to the b subunit of factor XIII. Our results show that fibrin clots made from 3/3' fibrinogen are resistant to fibrinolysis, but only if factor XIII is present during clotting. This suggests that the binding of factor XIII to 3' chains stabilizes clots, possibly by concentrating tile factor XIII at the surface of the growing fibrin matrix. We have therefore investigated the binding interactions of factor XIII and 3/3' fibrinogen. Sedimentation equilibrium analysis indicates that 2 3'/7' fibrinogen molecules can bind to each molecule of factor XIII, but that 3'/3' fibrinogen containing only - chains does not form detectable complexes. These results suggest the involvement of the C-terminal extension of the 3'' chain in binding factor XlII. GamierRobson analysis predicts that the C-terminal 20 residues of 3' fold into an a helix; helical wheel projections of this structure indicate that seven negativelycharged residues, including two tyrosine O-sulfates are clustered on one face of the helix. We propose that these residues mediate the interaction of i/, fibrinogen with factor XIII. Supported by funds from the A.It.A., PA Affiliate (to D.H.F. and M.G.F.) and the W.W. Smith Charitable Trust (to D.tt.F.).

Original languageEnglish (US)
Pages (from-to)A1264
JournalFASEB Journal
Volume11
Issue number9
StatePublished - Dec 1 1997

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ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

Cite this

Farrell, H., Fried, M. G., & Falls, L. A. (1997). Characterization of factor xiii-γ/γ fibrinogen complexesd. FASEB Journal, 11(9), A1264.