Structure, pathology and function of the N-linked sugar chains of human chorionic gonadotropin.
Human chorionic gonadotropin (hCG) contains five acidic N-linked sugar chains, which are derived from three neutral oligosaccharides by sialylation. Each of the two subunits (hCGalpha and hCGbeta) of hCG contain two glycosylated Asn residues. Glycopeptides, each containing a single glycosylated Asn, were obtained by digestion of hCGalpha with trypsin, and of hCGbeta with chymotrypsin and lysyl endopeptidase. Comparative study of the sugar chains of the four glycopeptides revealed the occurrence of site-directed glycosylation. Studies of the sugar chains of hCGs, purified from urine of patients with various trophoblastic diseases, revealed that choriocarcinoma hCGs contain sialylated or non-sialylated forms of eight neutral oligosaccharides. In contrast, hCGs from invasive mole patients contain sialyl derivatives of five neutral oligosaccharides. The structural characteristics of the five neutral oligosaccharides, detected in choriocarcinoma hCGs but not in normal placental hCGs, indicate that N-acetylglucosaminyltransferase IV (GnT-IV) is abnormally expressed in the malignant cells. This supposition was confirmed by molecular biological study of GnT-IV in placenta and choriocarcinoma cell lines. The appearance of tumor-specific sugar chains in hCG has been used to develop a diagnostic method of searching for malignant trophoblastic diseases. In addition, a summary of the current knowledge concerning the functional role of N-linked sugar chains in the expression of the hormonal activity of hCG has been presented.
Kobata
A
A
Tokyo Metropolitan Institute of Gerontology, Japan.
Takeuchi
M
M
D000818:Animals; D001665:Binding Sites; D050260:Carbohydrate Metabolism; D002240:Carbohydrate Sequence; D002241:Carbohydrates / Q000737:chemistry*; D002822:Choriocarcinoma; D006063:Chorionic Gonadotropin / Q000737:chemistry* / Q000378:metabolism; D002918:Chymotrypsin; D005260:Female; D006020:Glycopeptides / Q000737:chemistry; D006031:Glycosylation; D006801:Humans; D008969:Molecular Sequence Data; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics / Q000378:metabolism; D009844:Oligosaccharides / Q000032:analysis*; D011247:Pregnancy; D012697:Serine Endopeptidases; D014328:Trophoblastic Neoplasms / Q000175:diagnosis / Q000378:metabolism / Q000652:urine; D014357:Trypsin; D014407:Tumor Cells, Cultured; D014594:Uterine Neoplasms
D002241:Carbohydrates; D006063:Chorionic Gonadotropin; D006020:Glycopeptides; D009844:Oligosaccharides; D017351:N-Acetylglucosaminyltransferases; C038111:alpha-1,3-mannosylglycoprotein beta-1,4-N-acetylglucosaminyltransferase; D012697:Serine Endopeptidases; D002918:Chymotrypsin; D014357:Trypsin; C036813:lysyl endopeptidase