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Cited by 104Glycosylation and Glycoproteins ResearchPolysaccharides Composition and ApplicationsProteoglycans and glycosaminoglycans research

Function of the CysD domain of the gel-forming MUC2 mucin

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Ambort, Daniel, van der Post, Sjoerd, Johansson, Malin E. V., MacKenzie, Jenny, Thomsson, Elisabeth, Krengel, Ute, Hansson, Gunnar C.·2011·Biochemical Journal
DOI 10.1042/bj20102066PMC PMC3195396
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Abstract

The colonic human MUC2 mucin forms a polymeric gel by covalent disulfide bonds in its N- and C-termini. The middle part of MUC2 is largely composed of two highly O-glycosylated mucin domains that are interrupted by a CysD domain of unknown function. We studied its function as recombinant proteins fused to a removable immunoglobulin Fc domain. Analysis of affinity-purified fusion proteins by native gel electrophoresis and gel filtration showed that they formed oligomeric complexes. Analysis of the individual isolated CysD parts showed that they formed dimers both when flanked by two MUC2 tandem repeats and without these. Cleavages of the two non-reduced CysD fusion proteins and analysis by MS revealed the localization of all five CysD disulfide bonds and that the predicted C-mannosylated site was not glycosylated. All disulfide bonds were within individual peptides showing that the domain was stabilized by intramolecular disulfide bonds and that CysD dimers were of non-covalent nature. These observations suggest that CysD domains act as non-covalent cross-links in the MUC2 gel, thereby determining the pore sizes of the mucus.

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  • Non-covalent dimerization-probably by hydrophobic interactions-of domains of the colonic human MUC2 mucin containing cysteines has been identified.

    “Furthermore, non-covalent dimerization—probably by means of hydrophobic interactions—of domains of the colonic human MUC2 mucin containing cysteines has been identified [28].”

    From High level in vivo mucin-type glycosylation in Escherichia coli (2018) · cites this paper as [28]

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Authors
Ambort, D., van der Post, S., Johansson, M. E. V., MacKenzie, J., Thomsson, E., Krengel, U., & Hansson, G. C.
Affiliations
  • University of Gothenburg (SE)
  • Department of Medical Biochemistry, University of Gothenburg, Medicinaregatan 9A, SE-413 90 Gothenburg, Sweden
  • University of Oslo (NO)
Corresponding author
Hansson, Gunnar C.
ORCID
Venue
Biochemical Journal
Publisher
Portland Press Ltd.
Published
2011-04-27
Volume
436
Issue
1
Pages
61-70
ISSN
  • 0264-6021 (ISSN-L)
  • 1470-8728
DOI
10.1042/bj20102066
PMC
PMC3195396
OpenAlex
W2055237221
Cited by
104
References
0
Citations by year
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FWCI
3.61
Type
journal article
Language
en
Open access
Licence
Locations
  • Biochemical Journal (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • HAL (submittedVersion, other-oa)
  • Chalmers Research (Chalmers University of Technology) (submittedVersion)
  • Trinity's Access to Research Output (TARA) (Trinity College Dublin) (submittedVersion)
Funders
National Institute of Allergy and Infectious Diseases (U01AI095473)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glycosylation and Glycoproteins Research
  • Life Sciences › Agricultural and Biological Sciences › Food Science › Polysaccharides Composition and Applications
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Proteoglycans and glycosaminoglycans research
Keywords
MUC2, disulfide bonds, non-covalent crosslinking, C-mannosylation, colonic mucus, O-glycosylation, tandem repeats
MeSH terms
Amino Acid Sequence, Animals, Cricetulus, Disulfides, Electrophoresis, Polyacrylamide Gel, Glycosylation, Cricetinae, Humans, Molecular Sequence Data, Recombinant Fusion Proteins, CHO Cells, Protein Structure, Tertiary, Dimerization, Mucin-2

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