We have identified a γ-Arg–275 to His substitution in an abnormal fibrinogen designated
as “fibrinogen Saga” characterized by impaired fibrin monomer polymerization. By chromatofocusing
chromatography, we isolated normal and abnormal fragment Dl populations separately from the plasmic-calcium digests of fibrinogen derived from
the propositus, a heterozygote for the abnormality. We found that both normal and
abnormal fragment D1’s were similarly protected from digestion by plasmin in the presence of calcium ions
and further degraded to fragments D2 and D3 due to cleavage of the γ-chain remnant when calcium ions were replaced by chelating
agents. Abnormal fragment D1 failed to inhibit both thrombin-clotting of normal fibrinogen and polymerization
of normal fibrin monomer, while normal D1 exhibited marked inhibitory activities. In an aberrant peptide comprising residues
γ–274–302 isolated by HPLC from the lysyl endopeptidase-digests of abnormal fragment
D1, we identified a His substituting for an Arg at position 2, which corresponds to
position 275 of the mutant γ-chain
Keywords
Fibrinogen Saga - ɣ-Arg → His substitution - Dysfunctional fragment D
1
- Calcium protection from plasmin