Diversity of CysD domains in gel-forming mucins.
X-ray crystallography
adhesion
calcium binding
disulfide bonds
mucus
Journal
The FEBS journal
ISSN: 1742-4658
Titre abrégé: FEBS J
Pays: England
ID NLM: 101229646
Informations de publication
Date de publication:
11 2023
11 2023
Historique:
revised:
20
07
2023
received:
29
05
2023
accepted:
31
07
2023
medline:
2
11
2023
pubmed:
1
8
2023
entrez:
1
8
2023
Statut:
ppublish
Résumé
CysD domains are disulfide-rich modules embedded within long O-glycosylated regions of mucin glycoproteins. CysD domains are thought to mediate intermolecular adhesion during the intracellular bioassembly of mucin polymers and perhaps also after secretion in extracellular mucus hydrogels. The human genome encodes 18 CysD domains distributed across three different mucins. To date, experimental structural information is available only for the first CysD domain (CysD1) of the intestinal mucin MUC2, which is one of the most divergent of the CysDs. To provide experimental data on a CysD that is representative of a larger branch of the fold family, we determined the crystal structure of the seventh CysD domain (CysD7) from MUC5AC, a mucin found in the respiratory tract and stomach. The MUC5AC CysD7 structure revealed a single calcium-binding site, contrasting with the two sites in MUC2 CysD1. The MUC5AC CysD7 structure also contained an additional α-helix absent from MUC2 CysD1, with potential functional implications for intermolecular interactions. Lastly, the experimental structure emphasized the flexibility of the loop analogous to the main adhesion loop of MUC2 CysD1, suggesting that both sequence divergence and physical plasticity in this region may contribute to the adaptation of mucin CysD domains.
Substances chimiques
Mucins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
5196-5203Informations de copyright
© 2023 The Authors. The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.
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