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Unusual zymogen activation patterns in the protein corona of Ca-zeolites
Nature Catalysis ( IF 37.8 ) Pub Date : 2021-07-22 , DOI: 10.1038/s41929-021-00654-6
Xiaoqiang Shang 1 , Hao Chen 1 , Lisha Yu 1 , Liping Xiao 1 , Jie Fan 1 , Valentina Castagnola 2 , Kai Liu 2 , Luca Boselli 2 , Vanya Petseva 2 , Kenneth A. Dawson 2, 3 , Min He 4 , Fangjun Wang 4
Affiliation  

Zymogen (prothrombin) activation is central to the process of haemostasis (blood clotting) in the body, preventing serious blood loss and death from haemorrhagic shock. Zeolites comprise a family of crystalline microporous aluminosilicates that show increasing promise for use in massive bleeding control. However, the mechanism of zeolite-initiated haemostasis has remained unclear. Here, we investigate zeolite-initiated thrombin activation at the molecular level, and show that a prothrombinase complex can assemble on the inorganic surface of calcium-ion-exchanged zeolites (Ca-zeolites). Compared to natural platelet-based physiological processes, prothrombin-to-thrombin conversion on the surface of Ca-zeolite displays a striking thrombin activation pattern, with an exceptionally high plateau thrombin activity and at least 12-fold enhanced endogenous thrombin. The results provide a mechanistic understanding of how the zeolite surface functionally contributes to thrombin activation, paving the way towards the design of improved agents for bleeding management.



中文翻译:

钙沸石蛋白冠中不寻常的酶原活化模式

酶原(凝血酶原)激活是体内止血(凝血)过程的核心,可防止严重失血和失血性休克死亡。沸石包含一系列结晶微孔铝硅酸盐,它们显示出越来越多的用于控制大量出血的前景。然而,沸石引发的止血机制仍不清楚。在这里,我们在分子水平上研究了沸石引发的凝血酶活化,并表明凝血酶原复合物可以组装在钙离子交换沸石(Ca-沸石)的无机表面上。与天然的基于血小板的生理过程相比,钙沸石表面的凝血酶原到凝血酶的转化显示出惊人的凝血酶活化模式,具有异常高的高原凝血酶活性和至少 12 倍增强的内源性凝血酶。结果提供了对沸石表面如何在功能上促进凝血酶活化的机制理解,为设计用于出血管理的改进剂铺平了道路。

更新日期:2021-07-22
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