Abstract |
Protein O-glycosylation is an essential step for controlling structure and biological functions of glycoproteins involving differentiation, cell adhesion, immune response, inflammation, and tumorigenesis and metastasis. This study provides evidence of site-specific structural alteration induced during multiple sialylation at Ser/Thr residues of the tandem repeats in human MUC1 glycoprotein. Systematic nuclear magnetic resonance (NMR) study revealed that sialylation of the MUC1 tandem repeating glycopeptide, Pro-Pro-Ala- His-Gly-Val-Thr-Ser- Ala-Pro-Asp-Thr- Arg-Pro- Ala-Pro-Gly-Ser-Thr-Ala with core 2-type O- glycans at five potential glycosylation sites, afforded a specific conformational change at one of the most important cancer-relevant epitopes (Pro-Asp-Thr-Arg). This result indicates that disease-relevant epitope structures of human epithelial cell surface mucins can be altered both by the introduction of an inner GalNAc residue and by the distal sialylation in a peptide sequence-dependent manner. These data demonstrate the feasibility of NMR-based structural characterization of glycopeptides synthesized in a chemical and enzymatic manner in examining the conformational impact of the distal glycosylation at multiple O-glycosylation sites of mucin-like domains.
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Authors | Takahiko Matsushita, Naoki Ohyabu, Naoki Fujitani, Kentaro Naruchi, Hiroki Shimizu, Hiroshi Hinou, Shin-Ichiro Nishimura |
Journal | Biochemistry
(Biochemistry)
Vol. 52
Issue 2
Pg. 402-14
(Jan 15 2013)
ISSN: 1520-4995 [Electronic] United States |
PMID | 23259747
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antibodies, Monoclonal
- Epitopes
- MUC1 protein, human
- Mucin-1
- Peptides
- N-Acetylneuraminic Acid
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Topics |
- Amino Acid Sequence
- Antibodies, Monoclonal
(immunology)
- Antibody Affinity
- Epitopes
(chemistry, immunology)
- Glycosylation
- Humans
- Models, Molecular
- Molecular Sequence Data
- Mucin-1
(chemistry, immunology)
- N-Acetylneuraminic Acid
(chemistry, immunology)
- Neoplasms
(chemistry, immunology)
- Nuclear Magnetic Resonance, Biomolecular
- Peptides
(chemistry, immunology)
- Protein Conformation
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