4NCC

Neutralizing antibody to murine norovirus


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.49 Å
  • R-Value Free: 0.273 
  • R-Value Work: 0.204 
  • R-Value Observed: 0.207 

wwPDB Validation   3D Report Full Report


This is version 1.1 of the entry. See complete history


Literature

Flexibility in surface-exposed loops in a virus capsid mediates escape from antibody neutralization.

Kolawole, A.O.Li, M.Xia, C.Fischer, A.E.Giacobbi, N.S.Rippinger, C.M.Proescher, J.B.Wu, S.K.Bessling, S.L.Gamez, M.Yu, C.Zhang, R.Mehoke, T.S.Pipas, J.M.Wolfe, J.T.Lin, J.S.Feldman, A.B.Smith, T.J.Wobus, C.E.

(2014) J Virol 88: 4543-4557

  • DOI: https://doi.org/10.1128/JVI.03685-13
  • Primary Citation of Related Structures:  
    4NCC

  • PubMed Abstract: 

    New human norovirus strains emerge every 2 to 3 years, partly due to mutations in the viral capsid that allow escape from antibody neutralization and herd immunity. To understand how noroviruses evolve antibody resistance, we investigated the structural basis for the escape of murine norovirus (MNV) from antibody neutralization. To identify specific residues in the MNV-1 protruding (P) domain of the capsid that play a role in escape from the neutralizing monoclonal antibody (MAb) A6.2, 22 recombinant MNVs were generated with amino acid substitutions in the A'B' and E'F' loops. Six mutations in the E'F' loop (V378F, A382K, A382P, A382R, D385G, and L386F) mediated escape from MAb A6.2 neutralization. To elucidate underlying structural mechanisms for these results, the atomic structure of the A6.2 Fab was determined and fitted into the previously generated pseudoatomic model of the A6.2 Fab/MNV-1 virion complex. Previously, two distinct conformations, A and B, of the atomic structures of the MNV-1 P domain were identified due to flexibility in the two P domain loops. A superior stereochemical fit of the A6.2 Fab to the A conformation of the MNV P domain was observed. Structural analysis of our observed escape mutants indicates changes toward the less-preferred B conformation of the P domain. The shift in the structural equilibrium of the P domain toward the conformation with poor structural complementarity to the antibody strongly supports a unique mechanism for antibody escape that occurs via antigen flexibility instead of direct antibody-antigen binding.


  • Organizational Affiliation

    Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Fab fragment lightA [auth L],
C [auth 1]
211Mus musculusMutation(s): 0 
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Sequence Annotations
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  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Fab fragment heavyB [auth H],
D [auth 2]
221Mus musculusMutation(s): 0 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
Sequence Annotations
Expand
  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.49 Å
  • R-Value Free: 0.273 
  • R-Value Work: 0.204 
  • R-Value Observed: 0.207 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 42.59α = 90
b = 135.81β = 93.93
c = 83.31γ = 90
Software Package:
Software NamePurpose
SAINTdata scaling
SAINTdata reduction
PHENIXrefinement
PDB_EXTRACTdata extraction
PHASERphasing

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2014-02-19
    Type: Initial release
  • Version 1.1: 2014-04-09
    Changes: Database references