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Updated: Jun 2, 2026
08:58
Characterization of Glycoproteins with the Immunoglobulin Fold by X-Ray Crystallography and Biophysical Techniques
Published on: July 5, 2018
N-glycans modulate the function of human corticosteroid-binding globulin.
Zeynep Sumer-Bayraktar1, Daniel Kolarich, Matthew P Campbell
1Department of Biological Sciences and Chemistry and Biomolecular Sciences, Macquarie University, Sydney, NSW 2109, Australia.
Molecular & Cellular Proteomics : MCP
|May 12, 2011
Summary
The N-glycans on human corticosteroid-binding globulin (CBG) are crucial for its interaction with cell surface receptors. Removing these N-glycans and neuraminic acid residues significantly enhances CBG
Area of Science:
- Glycobiology
- Proteomics
- Endocrinology
Background:
- Human corticosteroid-binding globulin (CBG) is a key transporter of cortisol in circulation.
- CBG is heavily glycosylated, with six N-linked glycosylation sites, influencing its biological functions.
- The specific role of N-glycans in CBG's interaction with its receptor remains to be fully elucidated.
Purpose of the Study:
- To structurally and functionally characterize the N-glycosylation of human serum CBG.
- To investigate the biological importance of CBG N-glycans in mediating receptor interactions.
- To determine how N-glycan structure and terminal residues affect CBG's functional activity.
Main Methods:
- Liquid chromatography-tandem MS-based glycoproteomics and glycomics were employed.
- Exoglycosidase treatment was used to analyze N-glycan structures.
- Deglycosylated and desialylated CBG analogs were functionally tested using MCF-7 cells and cAMP production assays.
Main Results:
- Identified 26 complex N-glycoforms, predominantly bi- and tri-antennary, all terminated with neuraminic acid (NeuAc).
- High site occupancies (70.5-99.5%) and low core-fucosylation (0-34.9%) were observed across all six glycosylation sites.
- Removal of N-glycans and NeuAc residues significantly increased cAMP production, indicating enhanced CBG:receptor interaction.
Conclusions:
- CBG N-glycans play a significant role in modulating CBG's interaction with its cell surface receptor.
- Terminal NeuAc residues on N-glycans likely mediate this interaction through steric and/or electrostatic effects.
- Site-specific glycosylation patterns may influence CBG's accessibility and function.
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