7von
From Proteopedia
Native alpha-2-macroglobulin monomer
Structural highlights
FunctionA2MG_HUMAN Is able to inhibit all four classes of proteinases by a unique 'trapping' mechanism. This protein has a peptide stretch, called the 'bait region' which contains specific cleavage sites for different proteinases. When a proteinase cleaves the bait region, a conformational change is induced in the protein which traps the proteinase. The entrapped enzyme remains active against low molecular weight substrates (activity against high molecular weight substrates is greatly reduced). Following cleavage in the bait region a thioester bond is hydrolyzed and mediates the covalent binding of the protein to the proteinase. Publication Abstract from PubMedHuman 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. Cryo-EM structures reveal the dynamic transformation of human alpha-2-macroglobulin working as a protease inhibitor.,Huang X, Wang Y, Yu C, Zhang H, Ru Q, Li X, Song K, Zhou M, Zhu P Sci China Life Sci. 2022 Dec;65(12):2491-2504. doi: 10.1007/s11427-022-2139-2. , Epub 2022 Jun 28. PMID:35781771[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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