Cryo-EM structures reveal the dynamic transformation of human alpha-2-macroglobulin working as a protease inhibitor

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作者
Xiaoxing Huang
Youwang Wang
Cong Yu
Hui Zhang
Qiang Ru
Xinxin Li
Kai Song
Min Zhou
Ping Zhu
机构
[1] Chinese Academy of Sciences,National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics
[2] Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC),The Institute of Medicinal Plant Development
[3] University of Chinese Academy of Sciences,undefined
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alpha-2-macroglobulin; Cryo-EM; dynamic transformation; protease inhibitor; structure;
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摘要
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.
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页码:2491 / 2504
页数:13
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