TY - JOUR
T1 - High-resolution cryo-EM structures of outbreak strain human norovirus shells reveal size variations
AU - Jung, James
AU - Grant, Timothy
AU - Thomas, Dennis R.
AU - Diehnelt, Chris W.
AU - Grigorieff, Nikolaus
AU - Joshua-Tor, Leemor
N1 - Funding Information:
ACKNOWLEDGMENTS. We thank Kentucky BioProcessing (GI.1 Norwalk and GII.4 Minerva strains); Hugh S. Mason and Andrew G. Diamos (Biodesign Institute, Arizona State University; GII.2 SMV strain); and Robert L. Atmar (Baylor College of Medicine; GI.7 Houston strain) for producing the norovirus VLP samples. We thank Stephen C. Harrison, Stephen A. Johnston, and members of the L.J. lab for discussion and advice. D.R.T. and the cryo-EM facility are supported by the Cold Spring Harbor Laboratory. N.G. and L.J. are Investigators of the Howard Hughes Medical Institute.
Publisher Copyright:
© 2019 National Academy of Sciences. All rights reserved.
PY - 2019
Y1 - 2019
N2 - 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.
AB - 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.
KW - Cryo-EM
KW - Foodborne illnesses
KW - Norovirus
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U2 - 10.1073/pnas.1903562116
DO - 10.1073/pnas.1903562116
M3 - Article
C2 - 31182604
AN - SCOPUS:85068148143
SN - 0027-8424
VL - 116
SP - 12828
EP - 12832
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 26
ER -