{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Dulfer J"],"funding":["Swedish National Infrastructure for Computing","Deutsche Forschungsgemeinschaft","Leibniz-Gemeinschaft","Horizon 2020"],"pagination":["2125"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8067865"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["26(8)"],"pubmed_abstract":["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."],"journal":["Molecules (Basel, Switzerland)"],"pubmed_title":["Glycan-Induced Protein Dynamics in Human Norovirus P Dimers Depend on Virus Strain and Deamidation Status."],"pmcid":["PMC8067865"],"funding_grant_id":["SAW-2014-HPI-4","SNIC 2019/4-554 and 2020/5-100","FOR2327 ViroCarb","FET OPEN MS SPIDOC No. 801406"],"pubmed_authors":["Brodmerkel MN","Peters T","Dulfer J","Caleman C","Uetrecht C","Creutznacher R","Mallagaray A","Yan H","Marklund EG"],"additional_accession":[]},"is_claimable":false,"name":"Glycan-Induced Protein Dynamics in Human Norovirus P Dimers Depend on Virus Strain and Deamidation Status.","description":"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.","dates":{"release":"2021-01-01T00:00:00Z","publication":"2021 Apr","modification":"2026-04-29T23:40:14.167Z","creation":"2022-02-10T08:19:59.559Z"},"accession":"S-EPMC8067865","cross_references":{"pubmed":["33917179"],"doi":["10.3390/molecules26082125"]}}