Siebenlist K R, Meh D A, Mosesson M W
Department of Basic Health Sciences, School of Dentistry, Marquette University, Milwaukee, Wisconsin 53233, USA.
Biochemistry. 1996 Aug 13;35(32):10448-53. doi: 10.1021/bi9606206.
The difference between peak 1 and peak 2 fibrinogen lies in their gamma chains. Peak 1 molecules contain 2 gamma A chains; peak 2 molecules contain 1 gamma A and 1 gamma chain, the latter of which contains a 20 amino acid extension (gamma 408-427) replacing the carboxyl-terminal 4 amino acids of the gamma A chain (gamma A 408-411). While the existence of gamma chains in plasma fibrinogen molecules has been known for many years, their function remains unknown. When fibrinogen is purified from plasma, the factor XIII zymogen (A2B2) copurifies with it and is found only in the peak 2 fibrinogen when this fraction is separated from peak 1 fibrinogen by ion-exchange chromatography on DEAE-cellulose. Factor XIII alone applied to the same DEAE column elutes at a position between peak 1 and peak 2. When mixtures of peak 1 fibrinogen plus factor XIII or peak 2 fibrinogen plus factor XIII are applied to DEAE columns, the peak 1/factor XIII mixture elutes in two peaks, whereas the peak 2/factor XIII mixture elutes in the peak 2 fibrinogen position. Gel sieving on Superose 6 of peak 1/factor XIII mixtures results in two protein peaks, the first of which contains the fibrinogen. Most factor XIII activity elutes in the second peak with a small amount of activity emerging with the trailing end of the fibrinogen peak. Gel sieving of mixtures of peak 2 and factor XIII results in a single protein peak with all factor XIII activity emerging with the leading edge of the fibrinogen peak. The interaction between peak 2 fibrinogen and plasma factor XIII appears to be through binding to the B subunit of factor XIII since placental or platelet factor XIII (A2), which does not contain B subunits, elutes independently from peak 2 fibrinogen on DEAE-cellulose chromatography. The results indicate that peak 2 fibrinogen gamma chains have a physiologically significant affinity for the B subunits of plasma factor XIII and that through this interaction fibrinogen serves as a carrier for the plasma zymogen in circulating blood.
1型纤维蛋白原和2型纤维蛋白原的差异在于它们的γ链。1型分子含有2条γA链；2型分子含有1条γA链和1条γ链，后者含有一个20个氨基酸的延伸片段（γ408 - 427），取代了γA链的羧基末端4个氨基酸（γA 408 - 411）。虽然血浆纤维蛋白原分子中γ链的存在已为人所知多年，但其功能仍然未知。当从血浆中纯化纤维蛋白原时，因子XIII酶原（A2B2）与其共纯化，并且当通过DEAE - 纤维素离子交换色谱将该部分与1型纤维蛋白原分离时，仅在2型纤维蛋白原中发现。单独将因子XIII应用于相同的DEAE柱时，其在1型和2型之间的位置洗脱。当将1型纤维蛋白原加因子XIII或2型纤维蛋白原加因子XIII的混合物应用于DEAE柱时，1型/因子XIII混合物在两个峰中洗脱，而2型/因子XIII混合物在2型纤维蛋白原位置洗脱。对1型/因子XIII混合物在Superose 6上进行凝胶筛分产生两个蛋白质峰，第一个峰含有纤维蛋白原。大多数因子XIII活性在第二个峰中洗脱，少量活性在纤维蛋白原峰的尾部出现。对2型和因子XIII的混合物进行凝胶筛分产生一个单一的蛋白质峰，所有因子XIII活性在纤维蛋白原峰的前沿出现。2型纤维蛋白原与血浆因子XIII之间的相互作用似乎是通过与因子XIII的B亚基结合，因为胎盘或血小板因子XIII（A2）不含B亚基，在DEAE - 纤维素色谱上与2型纤维蛋白原独立洗脱。结果表明，2型纤维蛋白原γ链对血浆因子XIII的B亚基具有生理上显著的亲和力，并且通过这种相互作用，纤维蛋白原在循环血液中作为血浆酶原的载体。
