A functional assay suggests that heterodimers exist in two C-terminal gamma-chain dysfibrinogens: Matsumoto I and Vlissingen/Frankfurt IV.
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.
Hogan
K A
KA
Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill 27599-7525, USA.
Lord
S T
ST
Okumura
N
N
Terasawa
F
F
Galanakis
D K
DK
Scharrer
I
I
Gorkun
O V
OV
D000347:Afibrinogenemia / Q000097:blood / Q000235:genetics*; D019281:Dimerization; D015241:Fibrinogens, Abnormal / Q000737:chemistry*; D006579:Heterozygote; D006801:Humans; D007231:Infant, Newborn; D016297:Mutagenesis, Site-Directed; D055503:Protein Multimerization; D011993:Recombinant Fusion Proteins / Q000737:chemistry
D015241:Fibrinogens, Abnormal; D011993:Recombinant Fusion Proteins; C104703:fibrinogen Matsumoto I; C069866:fibrinogen Vlissingen