Huang Xiaoxing, Wang Youwang, Yu Cong, Zhang Hui, Ru Qiang, Li Xinxin, Song Kai, Zhou Min, Zhu Ping
National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
University of Chinese Academy of Sciences, Beijing, 100049, China.
Sci China Life Sci. 2022 Dec;65(12):2491-2504. doi: 10.1007/s11427-022-2139-2. Epub 2022 Jun 28.
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.
人α-2-巨球蛋白是一种广为人知的广谱蛋白酶抑制剂，在免疫、炎症和感染中发挥着重要作用。在此，我们报告了人α-2-巨球蛋白在天然状态、由其天然底物人胰蛋白酶诱导转化的状态以及天然状态和完全诱导状态之间的一系列中间状态下的冷冻电镜结构。这些结构呈现出不同的构象，揭示了作为蛋白酶抑制剂的α-2-巨球蛋白的动态转变。这些结果阐明了α-2-巨球蛋白捕获底物的分子机制。
