Structural analysis of the oligosaccharides derived from glycodelin, a human glycoprotein with potent immunosuppressive and contraceptive activities.
Glycodelin, also known as placental protein 14 (PP14) or progesterone-associated endometrial protein (PAEP), is a human glycoprotein with potent immunosuppressive and contraceptive activities. In this paper we report the first characterization of glycodelin-derived oligosaccharides. Using strategies based upon fast atom bombardment and electrospray mass spectrometry we have established that glycodelin is glycosylated at Asn-28 and Asn-63. The Asn-28 site carries high mannose, hybrid and complex-type structures, whereas the second site is exclusively occupied by complex-type glycans. The major non-reducing epitopes in the complex-type glycans are: Gal beta 1-4GlcNAc (lacNAc), GalNAc beta 1-4GlcNAc (lacdiNAc), NeuAc alpha 2-6Gal beta 1-4GlcNAc (sialylated lacNAc), NeuAc alpha 2-6Gal beta 1-4GlcNAc (sialylated lacdiNAc), Gal beta 1-4(Fuc alpha 1-3)GlcNAc (Lewisx), and GalNAc beta 1-4(Fuc alpha 1-3)GlcNAc (lacdiNAc analogue of Lewisx). It is possible that the oligosaccharides bearing sialylated lacNAc or lacdiNAc antennae may manifest immunosuppressive effects by specifically blocking adhesive and activation-related events mediated by CD22, the human B cell associated receptor. Oligosaccharides with fucosylated lacdiNAc antennae have previously been shown to potently block selectin-mediated adhesions and may perform the same function in glycodelin. The potent inhibitory effect of glycodelin on initial human sperm-zona pellucida binding is consistent with our previous suggestion that this cell adhesion event requires a selectin-like adhesion process. This result also raises the possibility that a convergence between immune and gamete recognition processes may have occurred in the types of carbohydrate ligands recognized in the human.
Dell
A
A
Department of Biochemistry, Imperial College of Science, Technology and Medicine, London, United Kingdom.
Morris
H R
HR
Easton
R L
RL
Panico
M
M
Patankar
M
M
Oehniger
S
S
Koistinen
R
R
Koistinen
H
H
Seppala
M
M
Clark
G F
GF
D000595:Amino Acid Sequence; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D003270:Contraceptive Agents; D003488:Cyanogen Bromide; D000939:Epitopes / Q000032:analysis / Q000737:chemistry; D008401:Gas Chromatography-Mass Spectrometry; D000071816:Glycodelin; D006023:Glycoproteins; D006801:Humans; D007166:Immunosuppressive Agents; D008969:Molecular Sequence Data; D009844:Oligosaccharides / Q000737:chemistry* / Q000302:isolation & purification; D010446:Peptide Fragments / Q000737:chemistry; D011257:Pregnancy Proteins / Q000737:chemistry*; D016339:Spectrometry, Mass, Fast Atom Bombardment
D003270:Contraceptive Agents; D000939:Epitopes; D000071816:Glycodelin; D006023:Glycoproteins; D007166:Immunosuppressive Agents; D009844:Oligosaccharides; C045246:PAEP protein, human; D010446:Peptide Fragments; D011257:Pregnancy Proteins; D003488:Cyanogen Bromide