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Nat Commun. 2019 Mar 21;10(1):1320. doi: 10.1038/s41467-019-09251-5.

A post-translational modification of human Norovirus capsid protein attenuates glycan binding.

Author information

1
Institute of Chemistry and Metabolomics, Center of Structural and Cell Biology in Medicine (CSCM), University of Lübeck, Ratzeburger Allee 160, 23562, Lübeck, Germany.
2
Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Martinistrasse 52, 20251, Hamburg, Germany.
3
Interfaculty Institute of BiochemistryUniversity of Tübingen, University of Tübingen, Hoppe-Seyler-Strasse 4, 72076, Tübingen, Germany.
4
Faculty of Pharmacy, Institute of Chemistry, San Pablo CEU University, Urb. Montepríncipe, 28668, Boadilla del Monte, Spain.
5
Department of Pharmacy, University of Copenhagen, Universitetsparken 2, Copenhagen, 2100, Denmark.
6
Institute of Molecular Systems Biology, ETH Zürich, Zürich, Switzerland.
7
European XFEL GmbH, Holzkoppel 4, 22869, Schenefeld, Germany.
8
Institute of Chemistry and Metabolomics, Center of Structural and Cell Biology in Medicine (CSCM), University of Lübeck, Ratzeburger Allee 160, 23562, Lübeck, Germany. thomas.peters@uni-luebeck.de.

Abstract

Attachment of human noroviruses to histo blood group antigens (HBGAs) is essential for infection, but how this binding event promotes the infection of host cells is unknown. Here, we employ protein NMR experiments supported by mass spectrometry and crystallography to study HBGA binding to the P-domain of a prevalent virus strain (GII.4). We report a highly selective transformation of asparagine 373, located in an antigenic loop adjoining the HBGA binding site, into an iso-aspartate residue. This spontaneous post-translational modification (PTM) proceeds with an estimated half-life of a few days at physiological temperatures, independent of the presence of HBGAs but dramatically affecting HBGA recognition. Sequence conservation and the surface-exposed position of this PTM suggest an important role in infection and immune recognition for many norovirus strains.

PMID:
30899001
PMCID:
PMC6428809
DOI:
10.1038/s41467-019-09251-5
[Indexed for MEDLINE]
Free PMC Article

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