PT - JOURNAL ARTICLE AU - Jung, James AU - Grant, Timothy AU - Thomas, Dennis R. AU - Diehnelt, Chris W. AU - Grigorieff, Nikolaus AU - Joshua-Tor, Leemor TI - High-resolution cryo-EM structures of outbreak strain human norovirus shells reveal size variations AID - 10.1101/580167 DP - 2019 Jan 01 TA - bioRxiv PG - 580167 4099 - http://biorxiv.org/content/early/2019/03/16/580167.short 4100 - http://biorxiv.org/content/early/2019/03/16/580167.full AB - Noroviruses are a leading cause of food-borne 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 (2.6-4.1 Å) cryo-electron 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. We developed a new asymmetric reconstruction method and resolved a metal ion adjacent to the co-receptor binding site, which affected the structural stability of the shell. Our structures serve as valuable templates for facilitating vaccine formulations.