Normal plasmic cleavage of the gamma-chain variant of "fibrinogen Saga" with an Arg-275 to His substitution.
We have identified a gamma-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 D1 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 gamma-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 gamma-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 gamma-chain.
Yamazumi
K
K
Division of Hemostasis and Thrombosis Research, Jichi Medical School, Tochigi-Ken, Japan.
Terukina
S
S
Onohara
S
S
Matsuda
M
M
D000293:Adolescent; D000595:Amino Acid Sequence; D001120:Arginine / Q000378:metabolism; D002118:Calcium / Q000494:pharmacology; D002845:Chromatography; D004533:Egtazic Acid / Q000494:pharmacology; D005260:Female; D005340:Fibrinogen / Q000302:isolation & purification; D015241:Fibrinogens, Abnormal / Q000378:metabolism*; D005341:Fibrinolysin / Q000378:metabolism*; D006639:Histidine / Q000378:metabolism; D006801:Humans; D008297:Male; D012697:Serine Endopeptidases / Q000378:metabolism
D015241:Fibrinogens, Abnormal; D006639:Histidine; D004533:Egtazic Acid; D005340:Fibrinogen; D001120:Arginine; D012697:Serine Endopeptidases; C036813:lysyl endopeptidase; D005341:Fibrinolysin; D002118:Calcium