Structure-Function Relationship of the Interaction between Tissue Factor and Factor VIIa.
Structure-Function Relationship of the Interaction between Tissue Factor and Factor VIIa.
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DOI：
10.1055/s-0035-1564044
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发表时间：
2015-10
影响因子：
5.7
通讯作者：
Morrissey JH
中科院分区：
文献类型：
--
作者：
Gajsiewicz JM;Morrissey JH
在止血和某些血栓性疾病中，组织因子和因子VIIa之间的相互作用是凝血的主要启动者。组织因子是一种广泛表达于血管外的完整膜蛋白，是凝血因子VIIa的调节蛋白辅因子。凝血因子VIIa是一种胰酶样丝氨酸蛋白酶，与其他凝血酶同源，在溶液中游离时活性较弱，必须结合其膜结合的辅因子才能发挥生理活性。组织因子通过活性部位定位、空间稳定和与底物的直接相互作用等多种机制来变构激活因子VIIa。组织因子、因子VIIa和底物之间的蛋白-膜相互作用在调节该酶复合体的活性方面都起着关键作用。此外，二价阳离子，如钙离子和镁离子，对于正确的蛋白质折叠以及蛋白质-膜和蛋白质-蛋白质相互作用都是至关重要的。本文讨论了这些因子对组织因子VIIa活性的影响。
Interactions between tissue factor and factor VIIa are the primary initiators of coagulation in hemostasis and certain thrombotic diseases. Tissue factor, an integral membrane protein expressed extensively outside of the vasculature, is the regulatory protein cofactor for coagulation factor VIIa. Factor VIIa, a trypsin-like serine protease homologous with other blood coagulation proteases, is weakly active when free in solution and must bind its membrane-bound cofactor for physiologically-relevant activity. Tissue factor allosterically activates factor VIIa by several mechanisms such as active site positioning, spatial stabilization, and direct interactions with the substrate. Protein-membrane interactions between tissue factor, factor VIIa, and substrates all play critical roles in modulating the activity of this enzyme complex. Additionally, divalent cations such as Ca2+ and Mg2+ are critical for correct protein folding, as well as protein-membrane and protein-protein interactions. The contributions of these factors towards tissue factor-factor VIIa activity are discussed in this review.