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TitleAtomic structure of the predominant GII.4 human norovirus capsid reveals novel stability and plasticity.
Journal, issue, pagesNat Commun, Vol. 13, Issue 1, Page 1241, Year 2022
Publish dateMar 10, 2022
AuthorsLiya Hu / Wilhelm Salmen / Rong Chen / Yi Zhou / Frederick Neill / James E Crowe / Robert L Atmar / Mary K Estes / B V Venkataram Prasad /
PubMed AbstractHuman noroviruses (HuNoVs) cause sporadic and epidemic viral gastroenteritis worldwide. The GII.4 variants are responsible for most HuNoV infections, and GII.4 virus-like particles (VLPs) are being ...Human noroviruses (HuNoVs) cause sporadic and epidemic viral gastroenteritis worldwide. The GII.4 variants are responsible for most HuNoV infections, and GII.4 virus-like particles (VLPs) are being used in vaccine development. The atomic structure of the GII.4 capsid in the native T = 3 state has not been determined. Here we present the GII.4 VLP structure with T = 3 symmetry determined using X-ray crystallography and cryo-EM at 3.0 Å and 3.8 Å resolution, respectively, which reveals unanticipated novel features. A novel aspect in the crystal structure determined without imposing icosahedral symmetry is the remarkable adaptability of the capsid protein VP1 driven by the flexible hinge between the shell and the protruding domains. In both crystal and cryo-EM structures, VP1 adopts a stable conformation with the protruding domain resting on the shell domain, in contrast to the 'rising' conformation observed in recent cryo-EM structures of other GII.4 VLPs. Our studies further revealed that the resting state of VP1 dimer is stabilized by a divalent ion, and chelation using EDTA increases capsid diameter, exposing new hydrophobic and antigenic sites and suggesting a transition to the rising conformation. These novel insights into GII.4 capsid structure, stability, and antigen presentation may be useful for ongoing vaccine development.
External linksNat Commun / PubMed:35273142 / PubMed Central
MethodsEM (single particle)
Resolution3.8 Å
Structure data

EMDB-23960, PDB-7mry:
Norovirus T=3 GII.4 HOV VLP
Method: EM (single particle) / Resolution: 3.8 Å

Chemicals

ChemComp-HOH:
WATER / Water

Source
  • norovirus gii.4
KeywordsVIRUS / T=3 Capsid GII.4 HOV Norovirus

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