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TitleAssembly Mechanism of Mucin and von Willebrand Factor Polymers.
Journal, issue, pagesCell, Vol. 183, Issue 3, Page 717-729.e16, Year 2020
Publish dateOct 29, 2020
AuthorsGabriel Javitt / Lev Khmelnitsky / Lis Albert / Lavi Shlomo Bigman / Nadav Elad / David Morgenstern / Tal Ilani / Yaakov Levy / Ron Diskin / Deborah Fass /
PubMed AbstractThe respiratory and intestinal tracts are exposed to physical and biological hazards accompanying the intake of air and food. Likewise, the vasculature is threatened by inflammation and trauma. Mucin ...The respiratory and intestinal tracts are exposed to physical and biological hazards accompanying the intake of air and food. Likewise, the vasculature is threatened by inflammation and trauma. Mucin glycoproteins and the related von Willebrand factor guard the vulnerable cell layers in these diverse systems. Colon mucins additionally house and feed the gut microbiome. Here, we present an integrated structural analysis of the intestinal mucin MUC2. Our findings reveal the shared mechanism by which complex macromolecules responsible for blood clotting, mucociliary clearance, and the intestinal mucosal barrier form protective polymers and hydrogels. Specifically, cryo-electron microscopy and crystal structures show how disulfide-rich bridges and pH-tunable interfaces control successive assembly steps in the endoplasmic reticulum and Golgi apparatus. Remarkably, a densely O-glycosylated mucin domain performs an organizational role in MUC2. The mucin assembly mechanism and its adaptation for hemostasis provide the foundation for rational manipulation of barrier function and coagulation.
External linksCell / PubMed:33031746 / PubMed Central
MethodsEM (single particle) / X-ray diffraction
Resolution1.63 - 3.7 Å
Structure data

10517

6tm2

7a5o

EMDB-10517, PDB-6tm2, PDB-7a5o:
Human MUC2 AAs 21-1397
Method: EM (single particle) / Resolution: 2.95 Å

EMDB-11658:
MUC2 amino terminal D1D2D3CysD1 2 bead map
Method: EM (single particle) / Resolution: 3.7 Å

PDB-6tm6:
MUC2 CysD1 domain
Method: X-RAY DIFFRACTION / Resolution: 1.63 Å

Chemicals

ChemComp-CA:
Unknown entry

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose / N-Acetylglucosamine

ChemComp-HOH:
WATER / Water

Source
  • homo sapiens (human)
KeywordsSTRUCTURAL PROTEIN / Glycoprotein / Extracellular / Polymer / CysD / mucin / calcium / disulfide / WXXW

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