6NS9

Crystal structure of the IVR-165 (H3N2) influenza virus hemagglutinin apo form


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.95 Å
  • R-Value Free: 0.193 
  • R-Value Work: 0.167 
  • R-Value Observed: 0.168 

wwPDB Validation   3D Report Full Report

Currently 6NS9 does not have a validation slider image.


This is version 2.1 of the entry. See complete history


Literature

Preventing an Antigenically Disruptive Mutation in Egg-Based H3N2 Seasonal Influenza Vaccines by Mutational Incompatibility.

Wu, N.C.Lv, H.Thompson, A.J.Wu, D.C.Ng, W.W.S.Kadam, R.U.Lin, C.W.Nycholat, C.M.McBride, R.Liang, W.Paulson, J.C.Mok, C.K.P.Wilson, I.A.

(2019) Cell Host Microbe 25: 836

  • DOI: https://doi.org/10.1016/j.chom.2019.04.013
  • Primary Citation of Related Structures:  
    6NS9, 6NSA, 6NSB, 6NSC, 6NSF, 6NSG

  • PubMed Abstract: 

    Egg-based seasonal influenza vaccines are the major preventive countermeasure against influenza virus. However, their effectiveness can be compromised when antigenic changes arise from egg-adaptive mutations on influenza hemagglutinin (HA). The L194P mutation is commonly observed in egg-based H3N2 vaccine seed strains and significantly alters HA antigenicity. An approach to prevent L194P would therefore be beneficial. We show that emergence of L194P during egg passaging can be impeded by preexistence of a G186V mutation, revealing strong incompatibility between these mutations. X-ray structures illustrate that individual G186V and L194P mutations have opposing effects on the HA receptor-binding site (RBS), and when both G186V and L194P are present, the RBS is severely disrupted. Importantly, wild-type HA antigenicity is maintained with G186V, but not L194P. Our results demonstrate that these epistatic interactions can be used to prevent the emergence of mutations that adversely alter antigenicity during egg adaptation.


  • Organizational Affiliation

    Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Hemagglutinin HA1 chain321Influenza A virus (A/Victoria/361/2011(H3N2))Mutation(s): 0 
Gene Names: HA
UniProt
Find proteins for L0HR89 (Influenza A virus)
Explore L0HR89 
Go to UniProtKB:  L0HR89
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupL0HR89
Sequence Annotations
Expand
  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Hemagglutinin HA2 chain176Influenza A virus (A/Victoria/361/2011(H3N2))Mutation(s): 0 
Gene Names: HA
UniProt
Find proteins for L0HR89 (Influenza A virus)
Explore L0HR89 
Go to UniProtKB:  L0HR89
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupL0HR89
Sequence Annotations
Expand
  • 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
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
D, F
2N-Glycosylation
Glycosylation Resources
GlyTouCan:  G42666HT
GlyCosmos:  G42666HT
GlyGen:  G42666HT
Entity ID: 5
MoleculeChains Length2D Diagram Glycosylation3D Interactions
beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose
E
3N-Glycosylation
Glycosylation Resources
GlyTouCan:  G15407YE
GlyCosmos:  G15407YE
GlyGen:  G15407YE
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.95 Å
  • R-Value Free: 0.193 
  • R-Value Work: 0.167 
  • R-Value Observed: 0.168 
  • Space Group: H 3 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 100.4α = 90
b = 100.4β = 90
c = 382.058γ = 120
Software Package:
Software NamePurpose
REFMACrefinement
HKL-2000data scaling
PHASERphasing

Structure Validation

View Full Validation Report

Currently 6NS9 does not have a validation slider image.



Entry History & Funding Information

Deposition Data


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

Revision History  (Full details and data files)

  • Version 1.0: 2019-04-24
    Type: Initial release
  • Version 1.1: 2019-06-19
    Changes: Data collection, Database references
  • Version 1.2: 2019-06-26
    Changes: Data collection, Database references
  • Version 1.3: 2019-12-18
    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: 2023-10-11
    Changes: Data collection, Database references, Derived calculations, Refinement description, Structure summary