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

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 and Katrine T. Schjoldager ()
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Thomas D. Madsen: University of Copenhagen
Lasse H. Hansen: University of Copenhagen
John Hintze: University of Copenhagen
Zilu Ye: University of Copenhagen
Shifa Jebari: Universidad del País Vasco
Daniel B. Andersen: Faculty of Health and Medical Sciences, University of Copenhagen
Hiren J. Joshi: University of Copenhagen
Tongzhong Ju: U.S. Food and Drug Administration
Jens P. Goetze: Rigshospitalet, University of Copenhagen
Cesar Martin: U.S. Food and Drug Administration
Mette M. Rosenkilde: Faculty of Health and Medical Sciences, University of Copenhagen
Jens J. Holst: Faculty of Health and Medical Sciences, University of Copenhagen
Rune E. Kuhre: Faculty of Health and Medical Sciences, University of Copenhagen
Christoffer K. Goth: University of Copenhagen
Sergey Y. Vakhrushev: University of Copenhagen
Katrine T. Schjoldager: University of Copenhagen

Nature Communications, 2020, vol. 11, issue 1, 1-13

Abstract: 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.

Date: 2020
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-17473-1

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DOI: 10.1038/s41467-020-17473-1

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