期刊
MOLECULES
卷 26, 期 8, 页码 -出版社
MDPI
DOI: 10.3390/molecules26082125
关键词
glycan interaction; norovirus capsid protein VP1; protruding domain; HDX-MS; native MS; hydrogen; deuterium exchange mass spectrometry
资金
- FOR2327 ViroCarb
- Leibniz Association [SAW-2014-HPI-4]
- Free and Hanseatic City of Hamburg
- Federal Ministry of Health
- High Performance Computing Center North (HPC2N) [2019/4-554, 2020/5-100]
- MS SPIDOC within the European Union's Horizon 2020 research and innovation program [801406]
Noroviruses are the main cause of viral gastroenteritis, with different strains showing strain-dependent glycan-induced protein dynamics, influenced by the prevalence in humans. Deamidation of N373 also plays a role in modulating glycan-mediated cell attachment in GII.4 strains, indicating a complex relationship between deamidation and glycan binding dynamics.
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.
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