|Entry||Database: PDB / ID: 7l5j|
|Title||Mouse Norovirus Protruding domain complexed with neutralizing Fab fragment from mAb A6.2|
|Keywords||VIRAL PROTEIN/IMMUNE SYSTEM / Antibody / norovirus / spike / VIRAL PROTEIN / VIRAL PROTEIN-IMMUNE SYSTEM complex|
|Function / homology||Calicivirus coat protein / Calicivirus coat protein C-terminal / Viral coat protein subunit / Picornavirus/Calicivirus coat protein / mitigation of host defenses by virus / Capsid protein|
Function and homology information
|Biological species||Murine norovirus 1|
Mus musculus (house mouse)
|Method||ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.2 Å|
|Authors||Smith, T.J. / Sherman, M.B.|
|Funding support|| United States, 1items |
|Citation||Journal: J Virol / Year: 2021|
Title: A norovirus uses bile salts to escape antibody recognition while enhancing receptor binding.
Authors: Alexis N Williams / Michael B Sherman / Hong Q Smith / Stefan Taube / B Montgomery Pettitt / Christiane E Wobus / Thomas J Smith /
Abstract: Noroviruses, members of the family, are the major cause of epidemic gastroenteritis in humans, causing ∼20 million cases annually. These plus-strand RNA viruses have T=3 icosahedral protein ...Noroviruses, members of the family, are the major cause of epidemic gastroenteritis in humans, causing ∼20 million cases annually. These plus-strand RNA viruses have T=3 icosahedral protein capsids with 90 pronounced protruding (P) domain dimers to which antibodies and cellular receptors bind. In the case of mouse norovirus (MNV), bile salts have been shown to enhance receptor (CD300lf) binding to the P domain. We previously demonstrated that the P domains of several genotypes are markedly flexible and 'float' over the shell, but the role of this flexibility was unclear. Recently, we demonstrated that bile causes a 90° rotation and collapse of the P domain on to the shell surface. Since bile binds distal to the P/shell interface, it was not at all clear how it could cause such dramatic changes. Here we present the near-atomic resolution cryo-EM structure of the protruding MNV complexed with a neutralizing Fab. Combined with previous results, we show here that bile salts cause allosteric conformational changes in the P domain that block antibody recognition to the top of the P domain. In addition, bile also causes a major rearrangement of the P domain dimers that are likely responsible for the bile-induced collapse of the P domain onto the shell. In the contracted shell conformation, antibodies to the P1 and shell domains are not expected to bind. Therefore, at the site of infection in the gut, the host's own bile allows the virus to escape antibody-mediated neutralization while enhancing cell attachment.The major feature of the Calicivirus capsids are the 90 protruding domains (P domains) that are the site of cell receptor(s) attachment and antibody epitopes. We previously demonstrated that these P domains are highly mobile and that bile causes these 'floating' P domains in mouse norovirus (MNV) to contract onto the shell surface. Here, we present the near atomic cryo-EM structure of the isolated MNV P domain complexed with a neutralizing Fab fragment. Together, the data shows that bile causes two sets of changes. First, bile causes allosteric conformational changes in the epitopes at the top of the P domain that block antibody binding. Second, bile causes the P domain dimer subunits to rotate relative to each other, causing contraction of the P domain that buries epitopes at the base of the P and shell domains. Collectively, MNV uses the host's own metabolites to enhance cell receptor binding while simultaneously blocking antibody recognition.
SummaryFull reportAbout validation report
|Structure viewer||Molecule: |
Downloads & links
A: Capsid protein
B: Capsid protein
L: Anti mouse norovirus mAb A6.2 Fab light chain
W: Anti mouse norovirus mAb A6.2 Fab heavy chain
X: Anti mouse norovirus mAb A6.2 Fab light chain
Y: Anti mouse norovirus mAb A6.2 Fab heavy chain
Mass: 34858.281 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Murine norovirus 1 / Production host: Escherichia coli (E. coli) / References: UniProt: Q2V8W4
Mass: 23083.512 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse)
Mass: 23759.061 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse)
|Experiment||Method: ELECTRON MICROSCOPY|
|EM experiment||Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction|
|Source (recombinant)||Organism: Escherichia coli (E. coli)|
|Details of virus||Empty: YES / Enveloped: NO / Isolate: SEROTYPE / Type: VIRION|
|Natural host||Organism: Mus musculus|
|Virus shell||Name: Protein Icosahedron / Triangulation number (T number): 3|
|Buffer solution||pH: 7.4|
|Specimen||Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES|
|Vitrification||Cryogen name: ETHANE|
-Electron microscopy imaging
Model: Titan Krios / Image courtesy: FEI Company
|Microscopy||Model: FEI TITAN KRIOS|
|Electron gun||Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM|
|Electron lens||Mode: BRIGHT FIELDBright-field microscopy|
|Image recording||Electron dose: 48 e/Å2 / Film or detector model: OTHER|
|Software||Name: PHENIX / Version: 1.15_3448: / Classification: refinement|
|CTF correction||Type: PHASE FLIPPING AND AMPLITUDE CORRECTION|
|3D reconstruction||Resolution: 3.2 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 1825383 / Symmetry type: POINT|
|Refine LS restraints|
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Novel coronavirus structure data
- International Committee on Taxonomy of Viruses (ICTV) defined the short name of the 2019 coronavirus as "SARS-CoV-2".
The species Severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2 - nature microbiology
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