Department of Pediatrics, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, United States.
Division of Rheumatology, Department of Medicine, University of Colorado School of Medicine, Aurora, CO, 80045, United States.
Biochem Biophys Res Commun. 2021 May 7;552:17-22. doi: 10.1016/j.bbrc.2021.02.134. Epub 2021 Mar 16.
Serine proteases are fundamental components of biology, including innate immunity, which is systematically orchestrated in an orderly, balanced fashion in the healthy host. Such serine proteases are found in two well-recognized pathways of an innate immune network, coagulation and complement. Both pathways, if uncontrolled due to a variety of causes, are pathogenic in numerous diseases, including coagulation disorders and infectious diseases. Previous studies have reported sequence homologies, functional similarities and interplay between these two pathways with some implications in health and disease. The current study newly reveals that complement component factor B (Bf), the second component of the alternative complement pathway, has thrombin-like activity, which is supported by a characteristic homology of the trypsin-like domain of Bf to that of thrombin. Moreover, we newly report that the trypsin-like domain of Bf is closely related to Limulus clotting factor C, the LPS sensitive clotting factor of the innate immune system. We will also discuss potential implications of our findings in diseases.
丝氨酸蛋白酶是生物学的基本组成部分,包括先天免疫系统,它在健康宿主中以有序、平衡的方式系统地进行协调。这种丝氨酸蛋白酶存在于先天免疫网络的两个公认途径中,即凝血和补体。由于各种原因,如果这两条途径不受控制,就会导致许多疾病,包括凝血障碍和传染病。以前的研究报告了这两条途径之间的序列同源性、功能相似性和相互作用,这些都对健康和疾病有一定的影响。本研究新发现补体成分因子 B(Bf),即替代补体途径的第二个成分,具有类凝血酶活性,这得到了 Bf 的类胰蛋白酶结构域与凝血酶的特征同源性的支持。此外,我们还新报告了 Bf 的类胰蛋白酶结构域与鲎凝固因子 C 密切相关,鲎凝固因子 C 是先天免疫系统中对 LPS 敏感的凝血因子。我们还将讨论我们的发现对疾病的潜在影响。