Kamura T, Tsuda H, Yae Y, Hattori S, Ohga S, Shibata Y, Kawabata S, Hamasaki N
Department of Clinical Chemistry and Laboratory Medicine, Kyushu University Faculty of Science, Fukuoka, Japan.
J Biol Chem. 1995 Dec 8;270(49):29392-9. doi: 10.1074/jbc.270.49.29392.
A dysfibrinogenemia was attributable to a single amino acid substitution from glycine to cysteine at residue 15 of the B beta chain in a fibrinogen molecule designated as fibrinogen Fukuoka II. The fibrinogen Fukuoka II showed prolonged thrombin and reptilase times and impaired fibrinopeptide B release by thrombin, resulting in abolition of fibrin monomer repolymerization under physiological conditions. Repolymerization of the des-(B beta 1-42)-fibrin monomers, however, was not distinguished from the normal pattern of des-(B beta 1-42)-fibrin monomers, suggesting that no other abnormality existed in fibrinogen Fukuoka II. Although an additional cysteine was substituted at residue 15 of the B beta chain, fibrinogen Fukuoka II had no free sulfhydryl group within the molecule. Instead, fibrinogen Fukuoka II formed a disulfide bond with cysteine, albumin, another mutated B beta chain within the same molecule, or intermolecular dimeric fibrinogen Fukuoka II. The mutation in fibrinogen Fukuoka II was the same as that in fibrinogen Ise published previously (Yoshida, N., Wada, H., Morita, K., Hirata, H., Matsuda, M., Yamazumi, K., Asakura, S., and Shirakawa, S. (1991) Blood 77, 1958-1963). Fibrinogen Ise, however, has been described as having prolonged thrombin time but normal reptilase time. Reasons for the discrepancy were not clear. Analysis of the B beta 1-42 fragment showed that fibrinogen was heterogeneous at position 31 of the B beta chain with respect to proline or hydroxyproline.
一种异常纤维蛋白原血症归因于在名为纤维蛋白原福冈II的纤维蛋白原分子Bβ链第15位残基处，甘氨酸被半胱氨酸单氨基酸取代。纤维蛋白原福冈II表现出凝血酶和蛇毒凝血酶时间延长，以及凝血酶介导的纤维蛋白肽B释放受损，导致在生理条件下纤维蛋白单体再聚合被抑制。然而，去（Bβ1 - 42）-纤维蛋白单体的再聚合与正常去（Bβ1 - 42）-纤维蛋白单体模式并无差异，这表明纤维蛋白原福冈II不存在其他异常。尽管在Bβ链第15位残基处额外取代了一个半胱氨酸，但纤维蛋白原福冈II分子内没有游离巯基。相反，纤维蛋白原福冈II与半胱氨酸、白蛋白、同一分子内另一条突变的Bβ链或分子间二聚体纤维蛋白原福冈II形成二硫键。纤维蛋白原福冈II中的突变与先前发表的纤维蛋白原伊势中的突变相同（吉田，N.，和田，H.，森田，K.，平田，H.，松田，M.，山津，K.，朝仓，S.，和白川，S.（1991年）《血液》77，1958 - 1963）。然而，纤维蛋白原伊势被描述为凝血酶时间延长但蛇毒凝血酶时间正常。差异的原因尚不清楚。对Bβ1 - 42片段的分析表明，纤维蛋白原在Bβ链第31位脯氨酸或羟脯氨酸位置上是异质的。
