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TitleCryo-EM structures reveal the dynamic transformation of human alpha-2-macroglobulin working as a protease inhibitor.
Journal, issue, pagesSci China Life Sci, Vol. 65, Issue 12, Page 2491-2504, Year 2022
Publish dateJun 28, 2022
AuthorsXiaoxing Huang / Youwang Wang / Cong Yu / Hui Zhang / Qiang Ru / Xinxin Li / Kai Song / Min Zhou / Ping Zhu /
PubMed AbstractHuman 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 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.
External linksSci China Life Sci / PubMed:35781771
MethodsEM (single particle)
Resolution3.9 - 8.0 Å
Structure data

32051

7von

EMDB-32051: native alpha-2-macroglobulin monomer
PDB-7von: Native alpha-2-macroglobulin monomer
Method: EM (single particle) / Resolution: 5.2 Å

32052

7voo

EMDB-32052, PDB-7voo:
Induced alpha-2-macroglobulin monomer
Method: EM (single particle) / Resolution: 3.9 Å

EMDB-32053: Macroglobulin family protein
Method: EM (single particle) / Resolution: 6.1 Å

EMDB-32054: Macroglobulin family protein
Method: EM (single particle) / Resolution: 6.9 Å

EMDB-32055: Macroglobulin family protein
Method: EM (single particle) / Resolution: 6.5 Å

EMDB-32057: Macroglobulin family protein
Method: EM (single particle) / Resolution: 8.0 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

Source
  • homo sapiens (human)
KeywordsBLOOD CLOTTING / protease inhibitor

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