Fibrinogen Matsumoto III: a Variant with γ275 Arg→Cys (CGC→TGC) – Comparison of Fibrin Polymerization Properties with those of Matsumoto I (γ364 Asp→His) and Matsumoto II (γ308 Asn→Lys)

Summary

Fibrinogen Matsumoto III (M-III) is a dysfibrinogen identified in a 66-year-old woman with rectal cancer. The fibrinogen level determined by the thrombin-time method was markedly decreased in preoperative coagulation tests of her plasma. Three fibrinogen polypeptide-chain gene fragments from the proposita were amplified by the polymerase chain reaction method, then sequenced. The triplet CGC encoding the amino acid residue γ275 was replaced by TGC, resulting in the substitution of Arg→Cys. There have been previous reports of nine families with the same alteration, nine families with an Arg→His variant and one family with an Arg→Ser variant in this residue, which has been shown to be one of the most important amino acids in the ’D:D’ interaction site. In addition, there are three silent mutations in the Aα-chain gene and two mutations in the intron of the Bβ-chain and the γ-chain gene. However, none of these mutations is thought to be the cause of the dysfunctional fibrinogen. The thrombin-catalyzed fibrin polymerization in the presence of 1 mM Ca ions was markedly delayed in purified M-III. Its lag period was longer than those of Matsumoto II (M-II; γ308Asn→Lys) and Matsumoto I (M-I; γ364Asp→His). γ364Asp is one of the most important residues in the polymerization pocket of the ’D:E’ interaction site and γ308Asn is located in the vicinity of a high affinity Ca²⁺ binding site in the D-domain, γ311-336. The maximum slope of the polymerization curve for M-III was about 4-fold steeper than that for M-I but less steep than that for M-II. These results may suggest that the tertiary structure of the polymerization pocket plays a more important role in the lateral aggregation of protofibrils than that of the ’D:D’ interaction site.

• References

• 1 Ebert RF.. Index of Variant Human Fibrinogens.. 1994 Edition, CRC Press, Inc.; Boca Raton, FL: 1994
• 2 Côté HCF, Lord ST, Pratt KP. γ-chain dysfibrinogenemias: molecular structure-function relationships of naturally occurring mutations in the γ chain of human fibrinogen.. Blood 1998; 92: 2195-212.
• 3 Niwa K, Kawata Y, Madoiwa S, Takebe M, Mimuro J, Sugo T, Matsuda M, Sugimoto T, Nose K. Fibrinogen Kamogawa: a new type of γArg-275 to Ser substitution characterized by delayed fibrin gel formation.. Thromb Haemost 1995; 73 suppl 1229
• 4 Mosesson MW, Siebenlist KR. The covalent structure of factor XIIIa crosslinked fibrinogen fibrils.. J Struct Biol 1995; 115: 88-101.
• 5 Mosesson MW, Siebenlist KR, DiOrio JP, Matsuda M, Hainfeld JF, Wall JS. The role of fibrinogen D domain intermolecular association sites in the polymerization of fibrin and fibrinogen Tokyo II (γ275 Arg→Cys).. J Clin Invest 1995; 96: 1053-8.
• 6 Spraggon G, Everse SJ, Doolittle RF. Crystal structures of fragment D from human fibrinogen and its crosslinked counterpart from fibrin.. Nature 1997; 389: 455-62.
• 7 Okumura N, Furihata K, Terasawa F. Nakagoshi R, Ueno I, Katsuyama T. Fibrinogen Matsumoto I; a γ364 Asp→His (GAT→CAT) substitution associated with defective fibrin polymerization.. Thromb Haemost 1996; 75: 887-91.
• 8 Okumura N, Furihata K, Terasawa F, Ishikawa S, Ueno I, Katsuyama T. Fibrinogen Matsumoto II: γ308 Asn→Lys (AAT→AAG) mutation associated with bleeding tendency.. Br J Haematol 1996; 94: 526-8.
• 9 Okumura N, Gorkun OV, Lord ST. Severely impaired polymerization of recombinant fibrinogen γ-364 Asp→His, the substitution discovered in a heterozygous individual.. J Biol Chem 1997; 272: 29596-601.
• 10 Takebe M, Soe G, Kohno I, Sugo T Matsuda M. Calcium ion-dependent monoclonal antibody against human fibrinogen; preparation, characterization, and application to fibrinogen purification.. Thromb Haemost 1995; 73: 662-7.
• 11 Mihalyi E. Physiological studies of bovine fibrinogen. IV. ultraviolet absorption and its relation to the structure of the molecule.. Biochemistry 1968; 7: 208-23.
• 12 Chung DW, Harris JE, Davie EW. Nucleotide sequences of the three genes coding for human fibrinogen.. In Fibrinogen, thrombosis, coagulation and fibrinolysis.. Liu CY, Chien S. (eds). Plenum Press; New York: 1990. pp 39-48.
• 13 Baumann RE, Henschen AH. Human fibrinogen polymorphic site analysis by restriction endonuclease digestion and allele-specific polymerase chain reaction amplification: Identification of polymorphisms at positions Aα312 and Bα448.. Blood 1993; 82: 2117-24.
• 14 Terukina S, Matsuda M, Hirata H, Takeda Y, Miyata T, Takao T, Shimonishi Y. Substitution of γ Arg-275 by Cys in an abnormal fibrinogen, “fibrinogen Osaka II” Evidence for a unique solitary cystine structure at the mutation site.. J Biol Chem 1988; 263: 13579-87.
• 15 Borrell M, Garí M, Coll I, Vallvé C, Tirado I, Soria JM, Sala N, Muñoz C, Oliver A, García A, Fontcuberta J. Abnormal polymerization and normal binding of plasminogen and t-PA in three new dysfibrinogenemias: Barcelona III and IV (γArg275→His) and Villajoyosa (γArg275→Cys).. Blood Coagulation Fibrinolysis 1995; 6: 198-206.
• 16 Niwa K. Studies on the mechanism of fibrin fiber formation-comparison among three hereditary dysfibrinogens with a γArg-275 to Ser, His, or Cys mutation-.. Jap J Thromb Hemosts 1997; 8: 33-43. (in Japanese).
• 17 Blombäck B, Hessel B, Hogg D, Therkildsen L. A two-step fibrinogen-fibrin transition in blood coagulation.. Nature 1978; 275: 501-5.
• 18 Weisel JW, Veklich Y, Gorkun O. The sequence of cleavage of fibrino-peptides from fibrinogen is important for protofibril formation and enhancement of lateral aggregation in fibrin clots.. J Mol Biol 1993; 232: 285-97.
• 19 Shainoff JR, Dardik BN. Fibrinopeptide B in fibrin assembly and metabolism; physiologic significance in delayed release of the peptide.. Ann NY Acad Sci 1983; 408: 254-68.
• 20 Hasegawa N, Sasaki S. Location of the binding site “b” for lateral polymerization of fibrin.. Thromb Res 1990; 57: 183-95.
• 21 Cierniewski CS, Budzynski AZ. Involvement of the α chain in fibrin clot formation. Effect of monoclonal antibodies.. Biochemistry 1992; 31: 4248-53.
• 22 Gorkun OV, Veklich I Y, Medved LV, Henschen AH, Weisel JW. Role of the αC domains of fibrin in clot formation.. Biochemistry 1994; 33: 6986-97.
• 23 Okada M, Blombäck B. Calcium and fibrin gel structure.. Thromb Res 1983; 29: 269-80.
• 24 Carr ME, Gabriel DA, McDonagh J. Influence of Ca ²⁺ on the structure of reptilase-derived and thrombin-derived fibrin gels.. Biochem J 1986; 239: 513-6.
• 25 Mihalyi E. Clotting of bovine fibrinogen. Kinetic analysis of the release of fibrinopeptides by thrombin and of the calcium uptake upon clotting at high fibrinogen concentration.. Biochemistry 1968; 7: 208-23.
• 26 Dang CV, Ebert RF, Bell WR. Localization of a fibrinogen calcium binding site between γ-subunit position 311 and 336 by terbium fluorescence.. J Biol Chem 1985; 260: 9713-9.
• 27 Weisel JW, Nagaswami C. Computer modeling of fibrin polymerization kinetics correlated with electron microscope and turbidity observations; clot structure and assembly are kinetically controlled.. Biophys J 1992; 63: 111-28.