- EMDB-8842: Mouse norovirus complexed with Fabs from the IgA, 2D3, that cross... -
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Basic information
Entry
Database: EMDB / ID: EMD-8842
Title
Mouse norovirus complexed with Fabs from the IgA, 2D3, that cross reacts with all tested strains
Map data
Mouse norovirus complexed with Fab from a cross-reactive IgA
Sample
Mouse norovirus complexed with Fabs from the IgA, 2D3 != Murine norovirus
Mouse norovirus complexed with Fabs from the IgA, 2D3
Virus: Murine norovirus
Function / homology
Function and homology information
T=3 icosahedral viral capsid / host cell cytoplasm / virus-mediated perturbation of host defense response / identical protein binding Similarity search - Function
Calicivirus coat protein C-terminal / Calicivirus coat protein C-terminal / Calicivirus coat protein / Calicivirus coat protein / Picornavirus/Calicivirus coat protein / Viral coat protein subunit Similarity search - Domain/homology
Journal: mSphere / Year: 2017 Title: Norovirus Escape from Broadly Neutralizing Antibodies Is Limited to Allostery-Like Mechanisms. Authors: Abimbola O Kolawole / Hong Q Smith / Sophia A Svoboda / Madeline S Lewis / Michael B Sherman / Gillian C Lynch / B Montgomery Pettitt / Thomas J Smith / Christiane E Wobus / Abstract: Ideal antiviral vaccines elicit antibodies (Abs) with broad strain recognition that bind to regions that are difficult to mutate for escape. Using 10 murine norovirus (MNV) strains and 5 human ...Ideal antiviral vaccines elicit antibodies (Abs) with broad strain recognition that bind to regions that are difficult to mutate for escape. Using 10 murine norovirus (MNV) strains and 5 human norovirus (HuNoV) virus-like particles (VLPs), we identified monoclonal antibody (MAb) 2D3, which broadly neutralized all MNV strains tested. Importantly, escape mutants corresponding to this antibody were very slow to develop and were distal to those raised against our previously studied antibody, A6.2. To understand the atomic details of 2D3 neutralization, we determined the cryo-electron microscopy (cryo-EM) structure of the 2D3/MNV1 complex. Interestingly, 2D3 binds to the top of the P domain, very close to where A6.2 binds, but the only escape mutations identified to date fall well outside the contact regions of both 2D3 and A6.2. To determine how mutations in distal residues could block antibody binding, we used molecular dynamics flexible fitting simulations of the atomic structures placed into the density map to examine the 2D3/MNV1 complex and these mutations. Our findings suggest that the escape mutant, V339I, may stabilize a salt bridge network at the P-domain dimer interface that, in an allostery-like manner, affects the conformational relaxation of the P domain and the efficiency of binding. They further highlight the unusual antigenic surface bound by MAb 2D3, one which elicits cross-reactive antibodies but which the virus is unable to alter to escape neutralization. These results may be leveraged to generate norovirus (NoV) vaccines containing broadly neutralizing antibodies. The simplest and most common way for viruses to escape antibody neutralization is by mutating residues that are essential for antibody binding. Escape mutations are strongly selected for by their effect on viral fitness, which is most often related to issues of protein folding, particle assembly, and capsid function. The studies presented here demonstrated that a broadly neutralizing antibody to mouse norovirus binds to an exposed surface but that the only escape mutants that arose were distal to the antibody binding surface. To understand this finding, we performed an analysis that suggested that those escape mutations blocked antibody binding by affecting structural plasticity. This kind of antigenic region-one that gives rise to broadly neutralizing antibodies but that the virus finds difficult to escape from-is therefore ideal for vaccine development.
History
Deposition
Jul 21, 2017
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Header (metadata) release
Aug 16, 2017
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Map release
Aug 16, 2017
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Update
Nov 28, 2018
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Current status
Nov 28, 2018
Processing site: RCSB / Status: Released
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Structure visualization
Movie
Surface view with section colored by density value
In the structure databanks used in Yorodumi, some data are registered as the other names, "COVID-19 virus" and "2019-nCoV". Here are the details of the virus and the list of structure data.
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