Evolutionary Conservation of the Sulfated Oligosaccharides on Vertebrate Glycoprotein Hormones That Control Circulatory Half-life (∗)

• Published in: The Journal of biological chemistry 1995-09, Vol.270 (37), p.21665-21671
• Main Authors: Manzella, Stephen M., Dharmesh, Shylaja M., Beranek, Mary C., Swanson, Penny, Baenziger, Jacques U.
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Biological Evolution; Carbohydrate Conformation; Carbohydrate Sequence; Chickens; Chorionic Gonadotropin - metabolism; Conserved Sequence; Glycoprotein Hormones, alpha Subunit - chemistry; Glycoprotein Hormones, alpha Subunit - metabolism; Half-Life; Humans; Luteinizing Hormone - chemistry; Luteinizing Hormone - metabolism; Molecular Sequence Data; N-Acetylgalactosaminyltransferases - metabolism; Oligosaccharides - chemistry; Oligosaccharides - isolation & purification; Oncorhynchus kisutch; Pituitary Gland - metabolism; Protein Structure, Secondary; Rana catesbeiana; Rats; Substrate Specificity; Sulfates - analysis; Transferrin - metabolism; Turtles; Vertebrates
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.270.37.21665

The circulatory half-life of the mammalian glycoprotein hormone lutropin is controlled by its unique Asn-linked oligosaccharides, which terminate with the sequence SO4-4-GalNAcβ1,4GlcNAc. A cluster of basic amino acids essential for recognition of the α subunit by the glycoprotein hormone:N-acetylgalactosaminyltransferase is located within two turns of an α helix (Mengeling, B. J., Manzella, S. M., and Baenziger, J. U.(1995) Proc. Natl. Acad. Sci. U. S. A. 92, 502-506). The amino acids within this region are virtually invariant in the α subunits of all vertebrates, indicating that the recognition determinant utilized by the N-acetylgalactosaminyltransferase has been conserved in species ranging from teleost fish to mammals. We demonstrate that the glycoprotein hormone:N-acetylgalactosaminyltransferase and the N-acetylgalactosamine-4-sulfotransferase responsible for the synthesis of these unique sulfated oligosaccharides are expressed in the pituitaries of vertebrates ranging from teleost fish to mammals. Furthermore, we show that Asn-linked oligosaccharides terminating with SO4-4-GalNAcβ1,4GlcNAc are present on the α and β subunits of the salmon glycoprotein hormone GTH II. Asn-linked oligosaccharides terminating with SO4-4-GalNAcβ1,4GlcNAc are unique structural features of the glycoprotein hormones that have been conserved during vertebrate evolution, suggesting they are critical for the expression of hormone biologic activity.