A new type of Ser substitution for gamma arg-275 in fibrinogen Kamogawa I characterized by impaired fibrin assembly

作者：Mimuro J; Kawata Y; Niwa K; Muramatsu S; Madoiwa S; Takano H; Sugo T; Sakata Y; Sugimoto T; Nose K; Matsuda M^*

来源：Thrombosis and Haemostasis, 1999, 81(6): 940-944.

DOI：10.1055/s-0037-1614603

A dew type of substitution, Arg to Ser at gamma 275, has been found in a heterozygous dysfibrinogen derived from a 23-year-old woman with no major bleeding or thrombosis. By sequence analyses of the affected gamma-chain and its gene, we found a single amino acid substitution of gamma Arg-275 to Ser in an aberrant gamma (274-302) residue peptide isolated from lysyl endopeptidase-digests of the patient's fibrinogen. In agreement with this amino acid substitution, we identified a single nucleotide exchange of A for C at position 5728 in the gamma-chain gene creating a codon (AGC) encoding Ser instead of the codon (CGC) encoding Arg at position gamma 275. Like two other known types of mutants with a His or Cys substitution at this position, the functional abnormality was characterized by delayed fibrin polymerization, most likely due to impaired abutting of two D domains of adjacent fibrin monomers in the same strand of fibrin protofibrils. The structural derangement that affects the D:D association may not be so severe as compared with those of Cys and His mutants, possessing an additional disulfide-linked Cys molecule and an imidazole ring at the mutation site, respectively.

• 出版日期1999-6