A functional assay suggests that heterodimers exist in two C-terminal gamma-chain dysfibrinogens: Matsumoto I and Vlissingen/Frankfurt IV

• Published in: Thrombosis and haemostasis Vol. 83; no. 4; p. 592
• Main Authors: Hogan, K A, Lord, S T, Okumura, N, Terasawa, F, Galanakis, D K, Scharrer, I, Gorkun, O V
• Format: Journal Article
• Language: English
• Published: Germany 01.04.2000
• Subjects: Afibrinogenemia - blood; Afibrinogenemia - genetics; Dimerization; Fibrinogens, Abnormal - chemistry; Heterozygote; Humans; Infant, Newborn; Mutagenesis, Site-Directed; Protein Multimerization; Recombinant Fusion Proteins - chemistry
• ISSN: 0340-6245
• DOI: 10.1055/s-0037-1613869

Because it contains three pairs of polypeptides, fibrinogen isolated from heterozygous individuals is expected to be a mixture of homodimers and heterodimers. Nevertheless, heterozygous individuals with only homodimers have been identified. We synthesized two recombinant fibrinogens with the mutations from fibrinogen Vlissingen/ Frankfurt IV (gamma(delta)319, 320) and Matsumoto I (gammaD364H), both identified in heterozygous individuals. We found that polymerization of these fibrinogens was undetectable in 30 min; polymerization of a 1:1 mixture of variant and normal fibrinogen was the same as polymerization of a 1:1 mixture of buffer and normal fibrinogen; polymerization of either plasma fibrinogen was markedly impaired when compared to the 1:1 mixture of the respective variant and normal fibrinogens. We conclude that each plasma fibrinogen is a mix of homodimers and heterodimers, such that the incorporation of heterodimers into the fibrin clot impairs polymerization. We suggest that incorporation of heterodimers can induce clinical symptoms.