Analysis of the role of oligosaccharides in the apoptotic activity of glycodelin A.
Glycodelin A, also known as placental protein-14, is a multifunctional glycosylated protein secreted by the uterine endometrium during the early phases of pregnancy. It is a known suppressor of T cell proliferation, inducer of T cell apoptosis, and inhibitor of sperm zona binding. Unlike in contraceptive activity, where the glycans on the molecule have been shown to play a crucial role, mutagenesis of the asparagines at sites of N-linked glycosylation (Asn(28) and Asn(63)) to glutamine shows that the apoptogenic activity of glycodelin A is executed by the protein backbone. Glycosylation at Asn(28) appears to play a role in the extracellular secretion of the molecule, as mutation of Asn(28) resulted in a significant decrease in the amount of secreted protein, and loss of both glycosylation sites reduced the secretion drastically. Our results also suggest that the loss of glycosylation does not affect the dimerization status of the molecule.
Jayachandran
Rajesh
R
Departments of Biochemistry and Microbiology and Cell Biology, Indian Institute of Science, Bangalore 560012, India.
Shaila
M S
MS
Karande
Anjali A
AA
D000328:Adult; D017209:Apoptosis / Q000502:physiology*; D001216:Asparagine; D019281:Dimerization; D005260:Female; D000071816:Glycodelin; D006023:Glycoproteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D019169:Jurkat Cells; D008297:Male; D008875:Middle Aged; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D011257:Pregnancy Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism / Q000473:pathology
D000071816:Glycodelin; D006023:Glycoproteins; C045246:PAEP protein, human; D011257:Pregnancy Proteins; D001216:Asparagine