RT Journal Article
SR Electronic
T1 Glycan-induced protein dynamics in human norovirus P dimers depend on virus strain and deamidation status
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.10.07.329623
DO 10.1101/2020.10.07.329623
A1 Jasmin Dülfer
A1 Hao Yan
A1 Maxim N Brodmerkel
A1 Robert Creutznacher
A1 Alvaro Mallagaray
A1 Thomas Peters
A1 Carl Caleman
A1 Erik G Marklund
A1 Charlotte Uetrecht
YR 2020
UL http://biorxiv.org/content/early/2020/10/07/2020.10.07.329623.abstract
AB 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.Competing Interest StatementThe authors have declared no competing interest.Asassolvent accessible areaCSPchemical shift perturbationESIelectrospray ionizationHBGAhisto-blood group antigenHDXhydrogen/deuterium exchangeiDiDfully deamidated (2x isoD373) P dimeriDNhalf deamidated (isoD373, native N373) P dimerKddissociation constantMDmolecular dynamicsNNfully native (2x native N373) P dimerP domainprotruding domainS domainshell domainSDS-PAGEsodium dodecyl sulfate polyacrylamide gel electrophoresisVLPvirus-like particleVP1major capsid protein