Molecular basis of recognition by the glycoprotein hormone-specific N-acetylgalactosamine-transferase.
Lutropin (LH) bears asparagine-linked oligosaccharides terminating with the unique sequence SO4-4GalNAc beta 1-4GlcNAc beta 1-2Man alpha, whereas follitropin (FSH) bears oligosaccharides terminating predominantly with the sequence Sia alpha-Gal beta 1-4GlcNAc beta 1-2Man alpha, where Sia is sialic acid. We previously identified a glycoprotein-hormone-specific N-acetylgalactosamine-transferase (GalNAc-transferase) that recognizes a peptide-recognition marker(s) present on the common glycoprotein hormone alpha subunit and beta subunits of human chorionic gonadotropin and LH but not on the beta subunit of FSH. We have now identified an amino acid sequence motif, Pro-Leu-Arg, that is essential for recognition by the GalNAc-transferase. This tripeptide sequence is found 6-9 residues on the amino-terminal side of a glycosylated asparagine on the alpha subunit and beta subunits of LH and human chorionic gonadotropin but is not present on the beta subunit of FSH. The presence of this motif accounts for the differences in LH and FSH oligosaccharide structures. Additional proteins containing this recognition motif have been identified and were determined to bear sulfated oligosaccharides with the same structures as those on the glycoprotein hormones, indicating that these structures are not restricted to the glycoprotein hormones.
Department of Pathology, Washington University School of Medicine, St. Louis, MO 63110.
P L
PL
Smith
J U
JU
Baenziger
D000595:Amino Acid Sequence; D000818:Animals; D001120:Arginine / Q000737:chemistry; D001667:Binding, Competitive; D002240:Carbohydrate Sequence; D002417:Cattle; D006063:Chorionic Gonadotropin / Q000378:metabolism; D005700:Galactosyltransferases / Q000378:metabolism*; D006020:Glycopeptides / Q000737:chemistry / Q000378:metabolism; D015292:Glycoprotein Hormones, alpha Subunit / Q000378:metabolism*; D007700:Kinetics; D008969:Molecular Sequence Data; D017350:N-Acetylgalactosaminyltransferases; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D010902:Pituitary Gland / Q000201:enzymology; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
D006063:Chorionic Gonadotropin; D006020:Glycopeptides; D015292:Glycoprotein Hormones, alpha Subunit; D010455:Peptides; D001120:Arginine; D005700:Galactosyltransferases; D017350:N-Acetylgalactosaminyltransferases; C072136:glycoprotein hormone-specific N-acetylgalactosamine transferase