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TitleThe intestinal MUC2 mucin C-terminus is stabilized by an extra disulfide bond in comparison to von Willebrand factor and other gel-forming mucins.
Journal, issue, pagesNat Commun, Vol. 14, Issue 1, Page 1969, Year 2023
Publish dateApr 8, 2023
AuthorsPablo Gallego / Maria-Jose Garcia-Bonete / Sergio Trillo-Muyo / Christian V Recktenwald / Malin E V Johansson / Gunnar C Hansson /
PubMed AbstractThe MUC2 mucin polymer is the main building unit of the intestinal mucus layers separating intestinal microbiota from the host epithelium. The MUC2 mucin is a large glycoprotein with a C-terminal ...The MUC2 mucin polymer is the main building unit of the intestinal mucus layers separating intestinal microbiota from the host epithelium. The MUC2 mucin is a large glycoprotein with a C-terminal domain similar to the MUC5AC and MUC5B mucins and the von Willebrand factor (VWF). A structural model of the C-terminal part of MUC2, MUC2-C, was generated by combining Cryo-electron microscopy, AlphaFold prediction, information of its glycosylation, and small angle X-ray scattering information. The globular VWD4 assembly in the N-terminal of MUC2-C is followed by 3.5 linear VWC domains that form an extended flexible structure before the C-terminal cystine-knot. All gel-forming mucins and VWF form tail-tail disulfide-bonded dimers in their C-terminal cystine-knot domain, but interestingly the MUC2 mucin has an extra stabilizing disulfide bond on the N-terminal side of the VWD4 domain, likely essential for a stable intestinal mucus barrier.
External linksNat Commun / PubMed:37031240 / PubMed Central
MethodsEM (single particle)
Resolution3.25 - 3.4 Å
Structure data

EMDB-13896, PDB-7qcl:
Structure of the MUCIN-2 Cterminal domains
Method: EM (single particle) / Resolution: 3.36 Å

EMDB-13897, PDB-7qcn:
Structure of the MUCIN-2 Cterminal domains: vWCN to TIL domains with a C2 symmetry
Method: EM (single particle) / Resolution: 3.4 Å

EMDB-13899, PDB-7qcu:
Structure of the MUCIN-2 Cterminal domains partially deglycosylated.
Method: EM (single particle) / Resolution: 3.25 Å

Chemicals

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

ChemComp-CA:
Unknown entry

Source
  • homo sapiens (human)
KeywordsSTRUCTURAL PROTEIN / Mucus / extracellular / net assemble

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