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
N1 - Funding Information:
T.P., B.S.B., T.S., and C.U. thank the Deutsche Forschungsgemeinschaft (DFG) for grants Pe494/12–1, BL1294/3–1, STE 1463/7–1, and UE 183/1–1, respectively (all three FOR2327, ViroCarb). We would like to thank Dr. Thorsten Biet for support with the NMR experiments, Dr. Hanne Peters for enzymatic synthesis of blood group B trisaccharide, and Prof. Javier Pérez Castells for providing us with blood group H disaccharide. We are grateful for support within the iNEXT program (PID 1483 and PID 2254) giving us access to the NMR high-field facilities at the Bijvoet Center in Utrecht. In particular, we would like to thank Dr. Hans Wienk from the Bijvoet Center for assisting us in any respect. We thank Dr. Mario Schubert (University of Salzburg, Austria) for helpful discussions. J.D. and C.U. would like to thank Prof. H. Schlüter (UKE, University of Hamburg, Germany) for access to high-resolution mass spectrometers and Dr. Daniel Kavan, Dr. Petr Man, and Dr. Alan Kádek for providing the DeutEx software. J.D. acknowledges funding from COST BM1403 and FOR2327 ViroCarb. C.U. acknowledges funding from the Leibniz Association through SAW-2014-HPI-4 grant.
Funding Information:
The Heinrich-Pette-Institute, Leibniz Institute for Experimental Virology is supported by the Freie und Hansestadt Hamburg and the Bundesministerium für Gesundheit (BMG). We thank Dr. Grant Hansman (University of Heidelberg, Germany) for providing us with the plasmids of the P-domains of GII.4 Saga, GII.10 Vietnam 026, and GII.17 Kawasaki 308. Prof. Dr. Stefan Taube (University of Lübeck, Germany) is thanked for providing the plasmid of the P-domain of GII.4 MI001. J.M.O. thanks to Fundación Universitaria San Pablo CEU for a mobility grant.
Publisher Copyright:
© 2019, The Author(s).
Copyright:
Copyright 2019 Elsevier B.V., All rights reserved.
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.
UR - http://www.scopus.com/inward/record.url?scp=85063320517&partnerID=8YFLogxK
U2 - 10.1038/s41467-019-09251-5
DO - 10.1038/s41467-019-09251-5
M3 - Journal articles
C2 - 30899001
AN - SCOPUS:85063320517
SN - 1751-8628
VL - 10
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 1320
ER -
