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首页> 外文期刊>Biochemistry >Interactions of human fibrinogens with factor XIII: roles of calcium and the gamma' peptide.
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Interactions of human fibrinogens with factor XIII: roles of calcium and the gamma' peptide.

机译:人类纤维蛋白原与因子XIII的相互作用:钙和γ'肽的作用。

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摘要

Plasma factor XIII is the zymogen of the transglutaminase factor XIIIa. This enzyme catalyzes the formation of isopeptide cross-links between fibrin molecules in nascent blood clots that greatly increase the mechanical stability of clots and their resistance to thrombolytic enzymes. We have characterized the solution interactions of factor XIII with two variants of fibrinogen, the soluble precursor of fibrin. Both the predominant fibrinogen gamma(A)/gamma(A) and the major variant gamma(A)/gamma' form complexes with a 2 fibrinogen:1 factor XIII ratio. The absence of detectable concentrations of 1:1 complexes in equilibrium mixtures containing free factor XIII and 2:1 complexes suggests that this interaction is cooperative. Factor XIII binds fibrinogen gamma(A)/gamma' approximately 20-fold more tightly than fibrinogen gamma(A)/gamma(A), and the interaction with fibrinogen gamma(A)/gamma' (but not fibrinogen gamma(A)/gamma(A)) is accompanied by a significant release of Ca(2+). Taken together, these results suggest that the strikingly anionic gamma' C-terminal sequence contains features that are important for factor XIII binding. Consistent with this notion, a synthetic 20-residue polypeptide containing the gamma' sequence was found to associate with factor XIII in a 2:1 molar ratio and act as an efficient competitor for fibrinogen gamma(A)/gamma' binding.
机译:血浆XIII因子是转谷氨酰胺酶XIIIa的酶原。这种酶催化新生血凝块中血纤蛋白分子之间异肽交联的形成,大大增加了凝块的机械稳定性及其对血栓溶解酶的抵抗力。我们已经表征了因子XIII与纤维蛋白原的两种变体(纤维蛋白的可溶性前体)的溶液相互作用。占主导地位的纤维蛋白原γ(A)/γ(A)和主要变异体γ(A)/ gamma'均以2的纤维蛋白原:1因子XIII比形成复合物。在含有游离因子XIII和2:1配合物的平衡混合物中,没有可检测浓度的1:1配合物,表明这种相互作用是协同的。因子XIII与血纤蛋白原gamma(A)/ gamma(A)的结合力约为20倍,与血纤蛋白原gamma(A)/ gamma'的结合力更强(但不与血纤蛋白原gamma(A)/ γ(A))伴随着Ca(2+)的大量释放。综上所述,这些结果表明,显着的阴离子γ'C末端序列包含对于因子XIII结合重要的特征。与该观点一致,发现含有γ′序列的合成的20残基多肽以2∶1的摩尔比与XIII因子缔合,并作为纤维蛋白原γ(A)/γ′结合的有效竞争者。

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