A post-translational modification of human Norovirus capsid protein attenuates glycan binding
Research output: Contribution to journal › Journal article › Research › peer-review
Final published version, 3.26 MB, PDF document
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.
|Number of pages||14|
|Publication status||Published - 21 Mar 2019|
- Asparagine/chemistry, Binding Sites, Blood Group Antigens/chemistry, Capsid Proteins/chemistry, Cloning, Molecular, Crystallography, X-Ray, Escherichia coli/genetics, Gene Expression, Genetic Vectors/chemistry, Host-Pathogen Interactions, Humans, Isoaspartic Acid/chemistry, Kinetics, Models, Molecular, Norovirus/genetics, Polysaccharides/chemistry, Protein Binding, Protein Conformation, alpha-Helical, Protein Conformation, beta-Strand, Protein Interaction Domains and Motifs, Protein Multimerization, Protein Processing, Post-Translational, Recombinant Proteins/chemistry
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