Evolutionary conservation of the sulfated oligosaccharides on vertebrate glycoprotein hormones that control circulatory half-life.
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-GalNAc beta 1,4GlcNAc. A cluster of basic amino acids essential for recognition of the alpha subunit by the glycoprotein hormone:N-acetylgalactosaminyltransferase is located within two turns of an alpha 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 alpha 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-GalNAc beta 1,4GlcNAc are present on the alpha and beta subunits of the salmon glycoprotein hormone GTH II. Asn-linked oligosaccharides terminating with SO4-4-GalNAc beta 1,4GlcNAc 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.
Manzella
S M
SM
Department of Pathology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Dharmesh
S M
SM
Beranek
M C
MC
Swanson
P
P
Baenziger
J U
JU
D000595:Amino Acid Sequence; D000818:Animals; D005075:Biological Evolution; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D002645:Chickens; D006063:Chorionic Gonadotropin / Q000378:metabolism; D017124:Conserved Sequence; D015292:Glycoprotein Hormones, alpha Subunit / Q000737:chemistry* / Q000378:metabolism*; D006207:Half-Life; D006801:Humans; D007986:Luteinizing Hormone / Q000737:chemistry* / Q000378:metabolism*; D008969:Molecular Sequence Data; D017350:N-Acetylgalactosaminyltransferases / Q000378:metabolism*; D009844:Oligosaccharides / Q000737:chemistry* / Q000302:isolation & purification; D017684:Oncorhynchus kisutch; D010902:Pituitary Gland / Q000378:metabolism*; D017433:Protein Structure, Secondary; D011892:Rana catesbeiana; D051381:Rats; D013379:Substrate Specificity; D013431:Sulfates / Q000032:analysis; D014168:Transferrin / Q000378:metabolism; D014426:Turtles; D014714:Vertebrates
D006063:Chorionic Gonadotropin; D015292:Glycoprotein Hormones, alpha Subunit; D009844:Oligosaccharides; D013431:Sulfates; D014168:Transferrin; D007986:Luteinizing Hormone; D017350:N-Acetylgalactosaminyltransferases; C072136:glycoprotein hormone-specific N-acetylgalactosamine transferase