PMID: 9449027

 

    Legend: Gene, Sites

Title : Carbohydrate and peptide structure of the alpha- and beta-subunits of human chorionic gonadotropin from normal and aberrant pregnancy and choriocarcinoma

Abstract :
  1. Human chorionic gonadotropin (hCG) , purified from the urine of 14 individuals with normal pregnancy, diabetic pregnancy, hydatidiform mole, or choriocarcinoma, plus two hCG standard preparations, was examined for concurrent peptide-sequence and asparagine (N)- and serine (O)-linked carbohydrate heterogeneity
  2. Protein-sequence analysis was used to measure amino-terminal heterogeneity and the "nicking" of internal peptide bonds
  3. The use of high-pH anion-exchange chromatography coupled with the increased sensitivity of pulsed amperometric detection (HPAE/PAD) revealed that distinct proportions of both hCG alpha- and beta-subunits from normal and aberrant pregnancy are hyperglycosylated, and that it is the extent of the specific subunit hyperglycosylation that significantly increases in malignant disease
  4. Peptide-bond nicking was restricted to a single linkage (beta 47-48) in normal and diabetic pregnancy, but occurred at two sites in standard preparations, at three sites in hydatidiform mole, and at three sites in choriocarcinoma beta- subunit
  5. In the carbohydrate moiety, alpha-subunit from normal pregnancy hCG contained nonfucosylated, mono- and biantennary N-linked structures (49.3 and 36.7%, means); fucosylated biantennary and triantennary oligosaccharides were also identified (7.3 and 6.9%)
  6. In choriocarcinoma alpha-subunit , the level of fucosylated biantennary increased, offset by a parallel decrease in the predominant biantennary structure of normal pregnancy (P < 0.0001)
  7. The beta- subunit from normal pregnancy hCG contained fucosylated and nonfucosylated biantennary N-linked structures; however, mono- and triantennary oligosaccharides were also identified (4.6 and 13.7%)
  8. For O-linked glycans, in beta- subunit from normal pregnancy, disaccharide-core structure predominated, whereas tetrasaccharide-core structure was also detected (15.6%)
  9. A trend was demonstrated in beta- subunit : the proportions of the nonpredominating N- and O-linked oligosaccharides increased stepwise from normal pregnancy to hydatidiform mole to choriocarcinoma
  10. The increases were: for monoantennary oligosaccharide, 4.6 to 6.8 to 11.2%; for triantennary, 13.7 to 26.7 to 51.5% and, for O-linked tetrasaccharide-core structure, 15.6 to 23.0 to 74.8%
  11. For hCG from individual diabetic pregnancy, the principal N-linked structure (34.7%) was consistent with a biantennary oligosaccharide previously reported only in carcinoma; and sialylation of both N- and O-linked antennae was significantly decreased compared to that of normal pregnancy
  12. Taken collectively, the distinctive patterns of subunit-specific, predominant oligosaccharides appear to reflect the steric effect of local protein structure during glycosylation processes
  13. The evidence of alternative or "hyperbranched" glycoforms on both alpha- and beta-subunits , seen at low levels in normal pregnancy and at increased or even predominant levels in malignant disease, suggests alternative substrate accessibility for Golgi processing enzymes , alpha 1,6 fucosyltransferase and N-acetylglucosaminyltransferase IV, in distinct proportions of subunit molecules
Output (sent_index, trigger, protein, sugar, site):
  • 0. beta-subunits, , beta-subunits, Carbohydrate and peptide structure, -
  • 0. peptide, , -, Carbohydrate and peptide structure, -
  • 11. sialylation, , -, both N- and O-linked antennae, -
  • 5. contained, , alpha-subunit, nonfucosylated, mono- and biantennary N-linked structures, -
  • 5. fucosylated, , -, fucosylated biantennary and triantennary oligosaccharides, -
  • 5. nonfucosylated, , -, nonfucosylated, mono- and biantennary N-linked structures, -
  • 7. contained, , subunit, fucosylated and nonfucosylated biantennary N-linked structures, -
  • 7. fucosylated, , -, fucosylated and nonfucosylated biantennary N-linked structures, -
  • 7. nonfucosylated, , -, fucosylated and nonfucosylated biantennary N-linked structures, -
Output(Part-Of) (sent_index, protein, site):
*Output_Site_Fusion* (sent_index, protein, sugar, site):

 

 

Protein NCBI ID SENTENCE INDEX
hCG alpha 1113 3
Human chorionic gonadotropin (hCG) 93659 1
alpha 1,6 fucosyltransferase 2530 13