Journal Article

High-resolution cryo-EM structures of outbreak strain human norovirus shells reveal size variations

Grant, Timothy, Thomas, Dennis R., Jung, James, Diehnelt, Chris W., Joshua-Tor, Leemor, Grigorieff, Nikolaus

2019

Overview

Noroviruses are a leading cause of foodborne illnesses worldwide. Although GII.4 strains have been responsible for most norovirus outbreaks, the assembled virus shell structures have been available in detail for only a single strain (GI.1). We present high-resolution (2.6- to 4.1-Å) cryoelectron microscopy (cryo-EM) structures of GII.4, GII.2, GI.7, and GI.1 human norovirus outbreak strain virus-like particles (VLPs). Although norovirus VLPs have been thought to exist in a single-sized assembly, our structures reveal polymorphism between and within genogroups, with small, medium, and large particle sizes observed. Using asymmetric reconstruction, we were able to resolve a Zn2+ metal ion adjacent to the coreceptor binding site, which affected the structural stability of the shell. Our structures serve as valuable templates for facilitating vaccine formulations.

• Publisher: National Academy of Sciences
• Subject: Binding sites / Biological Sciences / Biophysics and Computational Biology / Caliciviridae Infections - virology / Capsid - metabolism / Capsid - ultrastructure / Cryoelectron Microscopy / Disease Outbreaks / Foodborne diseases / Formulations / Genetic Variation / High resolution / Humans / Illnesses / Metal ions / Norovirus / Norovirus - genetics / Norovirus - isolation & purification / Norovirus - ultrastructure / Outbreaks / Polymorphism / Protein Binding / Shell stability / Structural stability / Virus-like particles / Viruses / Zinc / Zinc - metabolism