Oligosaccharides modulate the apoptotic activity of glycodelin
Rajesh Jayachandran1, Catherine M Radcliffe, Louise Royle
1Department of Biochemistry, Indian Institute of Science, Balgalore 560012, India.
Glycobiology
|July 21, 2006
Summary
Glycodelin (Gd) activity depends on its glycan structures. Different cell lines produce Gd with varying glycans, affecting its apoptogenic function, with glycan size influencing accessibility to the active region.
Area of Science:
- Reproductive biology
- Glycobiology
- Immunology
Background:
- GlycodelinA (GdA) is a pregnancy-associated glycoprotein with immunosuppressive and pro-apoptotic functions.
- GlycodelinS (GdS), a related glycoform, has different glycosylation and functions.
- GdA's apoptogenic activity is linked to its protein backbone and sialylation.
Purpose of the Study:
- To investigate how different glycan structures, produced by various expression systems, affect glycodelin's apoptogenic activity.
- To determine the role of glycan size and accessibility in modulating glycodelin's function.
Main Methods:
- Recombinant glycodelin (Gd) was expressed in Sf21, Tni, Chinese hamster ovary (CHO), and Pichia pastoris cell lines.
- Glycan structures of expressed Gd were analyzed.
- Apoptotic assays were performed on wild-type and glycosylation mutant Gd.
- Mannosidase digestion was used to assess the impact of glycan size.
Main Results:
- Recombinant Gd expressed in Sf21 cells showed apoptogenic activity, while Gd from Tni, CHO, and Pichia pastoris cells was inactive.
- Differences in glycan structures between Sf21- and Tni-expressed Gd correlated with their functional activity.
- Mannosidase digestion and analysis of glycosylation mutants indicated that glycan size influences the accessibility of the apoptogenic region.
Conclusions:
- The glycosylation pattern, specifically glycan size and structure, critically modulates glycodelin's apoptogenic activity.
- Cellular expression systems significantly impact glycodelin glycosylation and, consequently, its biological function.
- Glycan accessibility to the protein's apoptogenic domain is a key factor in determining glycodelin's functional outcome.
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