New Publication in Nature Communications
An atlas of O-linked glycosylation on peptide hormones reveals diverse biological roles
Authors: Thomas D. Madsen, Lasse H. Hansen, John Hintze, Zilu Ye, Shifa Jebari, Daniel B. Andersen, Hiren J. Joshi, Tongzhong Ju, Jens P. Goetze, Cesar Martin, Mette M. Rosenkilde, Jens J. Holst, Rune E. Kuhre, Christoffer K. Goth, Sergey Y. Vakhrushev & Katrine T. Schjoldager
Abstract:
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.
