Cryo-EM structures reveal the dynamic transformation of human alpha-2-macroglobulin working as a protease inhibitor
Cryo-EM structures reveal the dynamic transformation of human alpha-2-macroglobulin working as a protease inhibitor
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冷冻电镜结构揭示了人类 α-2-巨球蛋白作为蛋白酶抑制剂的动态转变
DOI：
10.1007/s11427-022-2139-2
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发表时间：
2022-06-28
影响因子：
9.1
通讯作者：
Zhu, Ping
中科院分区：
文献类型：
--
作者：
Huang, Xiaoxing;Wang, Youwang;Zhu, Ping
人α-2-巨球蛋白是一种众所周知的广谱蛋白酶抑制剂，在免疫、炎症和感染中起重要作用。在这里，我们报告的cryo-EM结构的人α-2-巨球蛋白在其天然状态，诱导状态转化其真实的基板，人胰蛋白酶，和一系列的中间状态之间的天然和完全诱导状态。这些结构表现出不同的构象，这揭示了作为蛋白酶抑制剂的α-2-巨球蛋白的动态转化。结果阐明了α-2-巨球蛋白包埋底物的分子机制。
Human alpha-2-macroglobulin is a well-known inhibitor of a broad spectrum of proteases and plays important roles in immunity, inflammation, and infections. Here, we report the cryo-EM structures of human alpha-2-macroglobulin in its native state, induced state transformed by its authentic substrate, human trypsin, and serial intermediate states between the native and fully induced states. These structures exhibit distinct conformations, which reveal the dynamic transformation of alpha-2-macro-globulin that acts as a protease inhibitor. The results shed light on the molecular mechanism of alpha-2-macroglobulin in entrapping substrates.