Glycan-induced protein dynamics in human norovirus P dimers depend on virus strain and deamidation status

Duelfer, J.; Yan, H.; Brodmerkel, M. N.; Creutznacher, R.; Mallagaray, A.; Peters, T.; Caleman, C.; Marklund, E. G.; Uetrecht, C.

doi:10.1101/2020.10.07.329623

bioRxiv · 10.1101/2020.10.07.329623

Glycan-induced protein dynamics in human norovirus P dimers depend on virus strain and deamidation status

Duelfer, J.·Yan, H.·Brodmerkel, M. N.·Creutznacher, R.·Mallagaray, A.·Peters, T.·Caleman, C.·Marklund, E. G.·Uetrecht, C.

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Abstract

Noroviruses are the major cause of 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. We also further examine structural effects of N373 deamidation upon glycan binding in partially deamidated GII.4 P dimers, which are likely present during infection. 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 population. Our results indicate that glycan binding induces strain-dependent structural dynamics, which are further altered by N373 deamidation, and hence hint at a role of deamidation in modulating cell attachment and entry in GII.4 strains.

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Duelfer, J., Yan, H., Brodmerkel, M. N., Creutznacher, R., Mallagaray, A., Peters, T., Caleman, C., Marklund, E. G., Uetrecht, C.. 2020-10-07. Glycan-induced protein dynamics in human norovirus P dimers depend on virus strain and deamidation status. https://doi.org/10.1101/2020.10.07.329623

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