TY - JOUR
T1 - An atlas of O-linked glycosylation on peptide hormones reveals diverse biological roles
AU - Madsen, Thomas D.
AU - Hansen, Lasse H.
AU - Hintze, John
AU - Ye, Zilu
AU - Jebari, Shifa
AU - Andersen, Daniel B.
AU - Joshi, Hiren J.
AU - Ju, Tongzhong
AU - Goetze, Jens P.
AU - Martin, Cesar
AU - Rosenkilde, Mette M.
AU - Holst, Jens J.
AU - Kuhre, Rune E.
AU - Goth, Christoffer K.
AU - Vakhrushev, Sergey Y.
AU - Schjoldager, Katrine T.
PY - 2020
Y1 - 2020
N2 - Peptide hormones and neuropeptides encompass a large class of bioactive peptides that regulate physiological processes like anxiety, blood glucose, appetite, inflammation and blood pressure. Here, we execute a focused discovery strategy to provide an extensive map of O-glycans on peptide hormones. We find that almost one third of the 279 classified peptide hormones carry O-glycans. Many of the identified O-glycosites are conserved and are predicted to serve roles in proprotein processing, receptor interaction, biodistribution and biostability. We demonstrate that O-glycans positioned within the receptor binding motifs of members of the neuropeptide Y and glucagon families modulate receptor activation properties and substantially extend peptide half-lives. Our study highlights the importance of O-glycosylation in the biology of peptide hormones, and our map of O-glycosites in this large class of biomolecules serves as a discovery platform for an important class of molecules with potential opportunities for drug designs.
AB - Peptide hormones and neuropeptides encompass a large class of bioactive peptides that regulate physiological processes like anxiety, blood glucose, appetite, inflammation and blood pressure. Here, we execute a focused discovery strategy to provide an extensive map of O-glycans on peptide hormones. We find that almost one third of the 279 classified peptide hormones carry O-glycans. Many of the identified O-glycosites are conserved and are predicted to serve roles in proprotein processing, receptor interaction, biodistribution and biostability. We demonstrate that O-glycans positioned within the receptor binding motifs of members of the neuropeptide Y and glucagon families modulate receptor activation properties and substantially extend peptide half-lives. Our study highlights the importance of O-glycosylation in the biology of peptide hormones, and our map of O-glycosites in this large class of biomolecules serves as a discovery platform for an important class of molecules with potential opportunities for drug designs.
U2 - 10.1038/s41467-020-17473-1
DO - 10.1038/s41467-020-17473-1
M3 - Journal article
C2 - 32820167
AN - SCOPUS:85089678360
VL - 11
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
M1 - 4033
ER -