Dataset Information

Interactions of human norovirus capsid P domain with histo-blood group antigens with Hydrogen-Deuterium Exchange Mass Spectrometry

ABSTRACT: 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 employed protein NMR experiments supported by mass spectrometry and crystallography to study HBGA binding to the P domain of a prevalent virus strain (GII.4) in more detail . We report a highly selective transformation of N373, 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.

INSTRUMENT(S): Orbitrap Fusion ETD

ORGANISM(S): Norovirus Hu/gii-4/saga4/2006/jp Norovirus Hu/gii/jp/2015/gii.p17_gii.17/kawasaki308 Norwalk Virus Norovirus Hu/gii.4/mi001/2011/usa

DISEASE(S): Acute Gastroenteritis

SUBMITTER: Jasmin Dülfer

LAB HEAD: Charlotte Uetrecht

PROVIDER: PXD011914 | Pride | 2019-03-20

REPOSITORIES: Pride

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Publications

A post-translational modification of human Norovirus capsid protein attenuates glycan binding.

Mallagaray Alvaro A Creutznacher Robert R Dülfer Jasmin J Mayer Philipp H O PHO Grimm Lena Lisbeth LL Orduña Jose Maria JM Trabjerg Esben E Stehle Thilo T Rand Kasper D KD Blaum Bärbel S BS Uetrecht Charlotte C Peters Thomas T

Nature communications 20190321 1

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 ...[more]

PMID: 30899001

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Project description:Noroviruses are non-enveloped (+) single stranded RNA viruses of the Caliciviridae family that cause an estimated 20 % of gastroenteritis cases worldwide . The virus possesses an icosahedral capsid, build by the two structural proteins VP1 and VP2. Noroviruses of genogroup II, especially GII.4, dominated in the majorities of outbreaks in the last two decades. In the last years, a novel GII.17 strain has also emerged in Asia. The major capsid protein VP1 builds dimers that are divided into the inner shell (S) domain and the outward-facing protruding (P) domain. The P domain is further divided into P1 and P2 subdomains, of which P2 is essential for host immune response and binds to histo blood-group antigens (HBGAs) for cell attachment in a strain-dependent manner, but the exact mechanism of cell attachment and entry remains unclear. Recently, a spontaneous deamidation of N373 with subsequent formation of an iso-aspartate (iD) was identified in GII.4 Saga P dimers that strongly attenuates glycan binding. This deamidation appears to be site specific and occurs in GII.4 MI001 P dimers as well, whereas it is absent in GII.10 Vietnam 026 and GII.17 Kawasaki 308 P dimers, which carry an Asp at the equivalent position. Given their high structural similarity with at the same time strain-dependent glycan binding behavior, we wanted to study if glycan binding induces different dynamic changes in P dimers of different strains using Hydrogen-Deuterium Exchange Mass Spectrometry (HDX-MS). Furthermore, we wanted to examine the structural effects of fucose binding to a mixture of wildtype and deamidated GII.4 MI001 and GII.4 Saga P dimers, to get more insights about the dynamic changes induced by N373 deamidation. Our results suggest identical glycan binding behavior of the almost identical GII.4 Saga and GII.4 MI001 strains, but reveal different glycan induced dynamics in GII.17 Kawasaki 308 and GII.10 Vietnam 026. Furthermore, all strains apart from GII.4 Saga form a second P domain species that is highly protected from HDX . In mixtures of wildtype and N373 deamidated GII.4 P dimers, fucose binding leads to different structural dynamics than in pure wildtype, indicating that the deamidated species could have a biological function in vivo.

Dataset Information

Interactions of human norovirus capsid P domain with histo-blood group antigens with Hydrogen-Deuterium Exchange Mass Spectrometry

Publications

A post-translational modification of human Norovirus capsid protein attenuates glycan binding.

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