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An atlas of O-linked glycosylation on peptide hormones reveals diverse biological roles

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  • 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
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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.

Original languageEnglish
Article number4033
JournalNature Communications
Volume11
Issue number1
ISSN2041-1723
DOIs
Publication statusPublished - 1 Dec 2020

ID: 60737382