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Article

Glycan-Induced Protein Dynamics in Human Norovirus P Dimers Depend on Virus Strain and Deamidation Status

1
Heinrich Pette Institute, Leibniz Institute for Experimental Virology, 20251 Hamburg, Germany
2
Department of Chemistry—BMC, Uppsala University, 75105 Uppsala, Sweden
3
Institute of Chemistry and Metabolomics, University of Lübeck, 23562 Lübeck, Germany
4
Department of Physics and Astronomy, Uppsala University, 75105 Uppsala, Sweden
5
Center for Free-Electron Laser Science, Deutsches Elektronen-Synchrotron, 22607 Hamburg, Germany
6
European XFEL GmbH, 22869 Schenefeld, Germany
*
Author to whom correspondence should be addressed.
Academic Editors: Pierluigi Luigi Mauri, Martina Marchetti-Deschmann and Diana Canetti
Molecules 2021, 26(8), 2125; https://doi.org/10.3390/molecules26082125
Received: 10 March 2021 / Revised: 29 March 2021 / Accepted: 31 March 2021 / Published: 7 April 2021
(This article belongs to the Special Issue Mass Spectrometric Proteomics II)
Noroviruses are the major cause of viral gastroenteritis and re-emerge worldwide every year, with GII.4 currently being the most frequent human genotype. The norovirus capsid protein VP1 is essential for host immune response. The P domain mediates cell attachment via histo blood-group antigens (HBGAs) in a strain-dependent manner but how these glycan-interactions actually relate to cell entry remains unclear. Here, hydrogen/deuterium exchange mass spectrometry (HDX-MS) is used to investigate glycan-induced protein dynamics in P dimers of different strains, which exhibit high structural similarity but different prevalence in humans. While the almost identical strains GII.4 Saga and GII.4 MI001 share glycan-induced dynamics, the dynamics differ in the emerging GII.17 Kawasaki 308 and rare GII.10 Vietnam 026 strain. The structural aspects of glycan binding to fully deamidated GII.4 P dimers have been investigated before. However, considering the high specificity and half-life of N373D under physiological conditions, large fractions of partially deamidated virions with potentially altered dynamics in their P domains are likely to occur. Therefore, we also examined glycan binding to partially deamidated GII.4 Saga and GII.4 MI001 P dimers. Such mixed species exhibit increased exposure to solvent in the P dimer upon glycan binding as opposed to pure wildtype. Furthermore, deamidated P dimers display increased flexibility and a monomeric subpopulation. Our results indicate that glycan binding induces strain-dependent structural dynamics, which are further altered by N373 deamidation, and hence hint at a complex role of deamidation in modulating glycan-mediated cell attachment in GII.4 strains. View Full-Text
Keywords: glycan interaction; norovirus capsid protein VP1; protruding domain; HDX-MS; native MS; hydrogen/deuterium exchange mass spectrometry glycan interaction; norovirus capsid protein VP1; protruding domain; HDX-MS; native MS; hydrogen/deuterium exchange mass spectrometry
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MDPI and ACS Style

Dülfer, J.; Yan, H.; Brodmerkel, M.N.; Creutznacher, R.; Mallagaray, A.; Peters, T.; Caleman, C.; Marklund, E.G.; Uetrecht, C. Glycan-Induced Protein Dynamics in Human Norovirus P Dimers Depend on Virus Strain and Deamidation Status. Molecules 2021, 26, 2125. https://doi.org/10.3390/molecules26082125

AMA Style

Dülfer J, Yan H, Brodmerkel MN, Creutznacher R, Mallagaray A, Peters T, Caleman C, Marklund EG, Uetrecht C. Glycan-Induced Protein Dynamics in Human Norovirus P Dimers Depend on Virus Strain and Deamidation Status. Molecules. 2021; 26(8):2125. https://doi.org/10.3390/molecules26082125

Chicago/Turabian Style

Dülfer, Jasmin, Hao Yan, Maxim N. Brodmerkel, Robert Creutznacher, Alvaro Mallagaray, Thomas Peters, Carl Caleman, Erik G. Marklund, and Charlotte Uetrecht. 2021. "Glycan-Induced Protein Dynamics in Human Norovirus P Dimers Depend on Virus Strain and Deamidation Status" Molecules 26, no. 8: 2125. https://doi.org/10.3390/molecules26082125

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