Biosynthesis of human fibrinogen. Subunit interactions and potential intermediates in the assembly

S. Huang, E. R. Mulvihill, D. H. Farrell, D. W. Chung, E. W. Davie

Research output: Contribution to journalArticle

82 Scopus citations

Abstract

Stable transfected baby hamster kidney (BHK) cells expressing human α, β, and γ fibrinogen chains together, in various combinations of any two, or individually, were established. Several types of subunit interactions were observed in the intracellular extracts of the transfected BHK cell lines as well as in Hep G2 cells. These included: 1) formation of αγ dimers linked by a disulfide bond(s), 2) formation of βγ dimers linked by a disulfide bond(s), 3) formation of αβγ half-molecules linked by disulfide bonds, and 4) formation of mature fibrinogen, which was also secreted into the cell culture medium. Analysis of the chain composition confirmed the stoichiometry of the αγ, βγ, and αβγ complexes. These data are consistent with the proposal that the αγ and βγ dimers as well as the αβγ half-molecules are intermediates in the assembly and biosynthesis of fibrinogen. In contrast, disulfide-linked αβ complexes were not found in transfected BHK cells or in Hep G2 cells, suggesting that the formation of disulfide bonds between these two chains most likely occurs when αβγ half-molecules are formed from αγ and/or βγ complexes and when αβγ half-molecules dimerize to generate the mature molecule. Dimers, trimers, and larger oligomers of each individual chain linked by disulfide bonds were also identified when each chain was expressed in the absence of the other two chains. Preferential formation of αγ and βγ complexes, rather than oligomers of individual chains, suggested that the oligomers were less likely to be intermediates in the assembly of fibrinogen. A model for fibrinogen assembly is presented based on these results.

Original languageEnglish (US)
Pages (from-to)8919-8926
Number of pages8
JournalJournal of Biological Chemistry
Volume268
Issue number12
StatePublished - Jan 1 1993

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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