Molecular basis of recognition by the glycoprotein hormone-specific N-acetylgalactosamine-transferase

Lutropin (LH) bears asparagine-linked oligosaccharides terminating with the unique sequence SO₄-4GalNAcβ1-4GlcNAcβ1-2Manα, whereas follitropin (FSH) bears oligosaccharides terminating predominantly with the sequence Siaα-Galβ1-4GlcNAcβ1-2Manα, 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 α subunit and β subunits of human chorionic gonadotropin and LH but not on the β 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 a subunit and β subunits of LH and human chorionic gonodatropin but is not present on the β 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.