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TitleStructure of the MUC5AC VWD3 assembly responsible for the formation of net-like mucin polymers.
Journal, issue, pagesEMBO Rep, Vol. 26, Issue 6, Page 1457-1471, Year 2025
Publish dateFeb 27, 2025
AuthorsSergio Trillo-Muyo / Anna Ermund / Gunnar C Hansson /
PubMed AbstractGel-forming mucins MUC5AC and MUC5B constitute the main structural component of the mucus in the respiratory system. Secreted mucins interact specifically with each other and other molecules giving ...Gel-forming mucins MUC5AC and MUC5B constitute the main structural component of the mucus in the respiratory system. Secreted mucins interact specifically with each other and other molecules giving mucus specific properties. We determined the cryoEM structures of the wild type D3 assembly of the human MUC5AC mucin and the structural single nucleotide polymorphisms (SNP) variants Arg996Gln and Arg1201Trp that affect intermolecular interactions. Our structures explain the MUC5AC N-terminal non-covalent oligomerization after secretion. The D3 assembly forms covalent dimers that can appear in two alternative conformations, open and closed, where the closed conformation dimers interact through an arginine-rich loop in the TIL3 domain to form tetramers. Our study provides a model to explain MUC5AC net-like structures and how the two SNPs will affect mucus organization, something that might affect lung and other diseases.
External linksEMBO Rep / PubMed:40016425 / PubMed Central
MethodsEM (single particle)
Resolution2.94 - 3.69 Å
Structure data

EMDB-18638, PDB-8qsp:
MUC5AC D3 assembly. SNP rs36189285: Arg996Gln.
Method: EM (single particle) / Resolution: 3.69 Å

EMDB-18648, PDB-8qtb:
MUC5AC D'D3CysD1 domains. SNP rs36189285: Arg996Gln.
Method: EM (single particle) / Resolution: 2.94 Å

EMDB-18654, PDB-8qtv:
MUC5AC D'D3CysD1 domains.
Method: EM (single particle) / Resolution: 3.25 Å

EMDB-18828, PDB-8r1u:
MUC5AC D3 assembly. SNP rs878913005: Arg1201Trp.
Method: EM (single particle) / Resolution: 3.19 Å

EMDB-18829, PDB-8r1z:
MUC5AC D3 assembly. SNPs rs36189285, rs878913005: Arg996Gln, Arg1201Trp.
Method: EM (single particle) / Resolution: 3.2 Å

Chemicals

ChemComp-CA:
Unknown entry

Source
  • homo sapiens (human)
KeywordsSTRUCTURAL PROTEIN / gelforming glycoprotein / Mucin

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