TY - JOUR
T1 - A post-translational modification of human Norovirus capsid protein attenuates glycan binding
AU - Mallagaray, Alvaro
AU - Creutznacher, Robert
AU - Dülfer, Jasmin
AU - Mayer, Philipp H O
AU - Grimm, Lena Lisbeth
AU - Orduña, Jose Maria
AU - Trabjerg, Esben
AU - Stehle, Thilo
AU - Rand, Kasper D
AU - Blaum, Bärbel S
AU - Uetrecht, Charlotte
AU - Peters, Thomas
PY - 2019/12/1
Y1 - 2019/12/1
N2 - 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.
AB - 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.
KW - Asparagine/chemistry
KW - Binding Sites
KW - Blood Group Antigens/chemistry
KW - Capsid Proteins/chemistry
KW - Cloning, Molecular
KW - Crystallography, X-Ray
KW - Escherichia coli/genetics
KW - Gene Expression
KW - Genetic Vectors/chemistry
KW - Host-Pathogen Interactions
KW - Humans
KW - Isoaspartic Acid/chemistry
KW - Kinetics
KW - Models, Molecular
KW - Norovirus/genetics
KW - Polysaccharides/chemistry
KW - Protein Binding
KW - Protein Conformation, alpha-Helical
KW - Protein Conformation, beta-Strand
KW - Protein Interaction Domains and Motifs
KW - Protein Multimerization
KW - Protein Processing, Post-Translational
KW - Recombinant Proteins/chemistry
U2 - 10.1038/s41467-019-09251-5
DO - 10.1038/s41467-019-09251-5
M3 - Journal article
C2 - 30899001
SN - 2041-1723
VL - 10
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 1320
ER -