6AOP

Crystal structure of the A/Brisbane/10/2007 (H3N2) influenza virus hemagglutinin L194P mutant apo form


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.30 Å
  • R-Value Free: 0.232 
  • R-Value Work: 0.197 
  • R-Value Observed: 0.199 

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This is version 2.1 of the entry. See complete history


Literature

A structural explanation for the low effectiveness of the seasonal influenza H3N2 vaccine.

Wu, N.C.Zost, S.J.Thompson, A.J.Oyen, D.Nycholat, C.M.McBride, R.Paulson, J.C.Hensley, S.E.Wilson, I.A.

(2017) PLoS Pathog 13: e1006682-e1006682

  • DOI: https://doi.org/10.1371/journal.ppat.1006682
  • Primary Citation of Related Structures:  
    6AOP, 6AOQ, 6AOR, 6AOS, 6AOT, 6AOU, 6AOV

  • PubMed Abstract: 

    The effectiveness of the annual influenza vaccine has declined in recent years, especially for the H3N2 component, and is a concern for global public health. A major cause for this lack in effectiveness has been attributed to the egg-based vaccine production process. Substitutions on the hemagglutinin glycoprotein (HA) often arise during virus passaging that change its antigenicity and hence vaccine effectiveness. Here, we characterize the effect of a prevalent substitution, L194P, in egg-passaged H3N2 viruses. X-ray structural analysis reveals that this substitution surprisingly increases the mobility of the 190-helix and neighboring regions in antigenic site B, which forms one side of the receptor binding site (RBS) and is immunodominant in recent human H3N2 viruses. Importantly, the L194P substitution decreases binding and neutralization by an RBS-targeted broadly neutralizing antibody by three orders of magnitude and significantly changes the HA antigenicity as measured by binding of human serum antibodies. The receptor binding mode and specificity are also altered to adapt to avian receptors during egg passaging. Overall, these findings help explain the low effectiveness of the seasonal vaccine against H3N2 viruses, and suggest that alternative approaches should be accelerated for producing influenza vaccines as well as isolating clinical isolates.


  • Organizational Affiliation

    Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, United States of America.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Hemagglutinin HA1 chain323Influenza A virus (A/Brisbane/10/2007(H3N2))Mutation(s): 0 
Gene Names: HA
UniProt
Find proteins for I6UCL3 (Influenza A virus)
Explore I6UCL3 
Go to UniProtKB:  I6UCL3
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupI6UCL3
Sequence Annotations
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  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Hemagglutinin HA2 chain174Influenza A virus (A/Brisbane/10/2007(H3N2))Mutation(s): 0 
Gene Names: HA
UniProt
Find proteins for C3PR70 (Influenza A virus)
Explore C3PR70 
Go to UniProtKB:  C3PR70
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupC3PR70
Sequence Annotations
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  • Reference Sequence
Oligosaccharides

Help

Entity ID: 3
MoleculeChains Length2D Diagram Glycosylation3D Interactions
alpha-D-mannopyranose-(1-3)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose
C, D
4N-Glycosylation
Glycosylation Resources
GlyTouCan:  G81315DD
GlyCosmos:  G81315DD
GlyGen:  G81315DD
Entity ID: 4
MoleculeChains Length2D Diagram Glycosylation3D Interactions
2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose
E
2N-Glycosylation
Glycosylation Resources
GlyTouCan:  G42666HT
GlyCosmos:  G42666HT
GlyGen:  G42666HT
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.30 Å
  • R-Value Free: 0.232 
  • R-Value Work: 0.197 
  • R-Value Observed: 0.199 
  • Space Group: H 3 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 100.491α = 90
b = 100.491β = 90
c = 383.319γ = 120
Software Package:
Software NamePurpose
REFMACrefinement
HKL-2000data processing
HKL-2000data scaling
PHASERphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)United StatesR56 AI117675
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)United StatesR56 AI127371
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)United StatesR01 AI114730

Revision History  (Full details and data files)

  • Version 1.0: 2017-10-18
    Type: Initial release
  • Version 1.1: 2017-11-08
    Changes: Database references
  • Version 1.2: 2019-12-11
    Changes: Author supporting evidence
  • Version 2.0: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Atomic model, Data collection, Derived calculations, Structure summary
  • Version 2.1: 2023-10-04
    Changes: Data collection, Database references, Derived calculations, Refinement description, Structure summary