6BKQ

Crystal structure of the A/Hong Kong/1/1968 (H3N2) influenza virus hemagglutinin E190D mutant in complex with 6'-SLN


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.25 Å
  • R-Value Free: 0.208 
  • R-Value Work: 0.178 
  • R-Value Observed: 0.179 

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This is version 2.1 of the entry. See complete history


Literature

A complex epistatic network limits the mutational reversibility in the influenza hemagglutinin receptor-binding site.

Wu, N.C.Thompson, A.J.Xie, J.Lin, C.W.Nycholat, C.M.Zhu, X.Lerner, R.A.Paulson, J.C.Wilson, I.A.

(2018) Nat Commun 9: 1264-1264

  • DOI: https://doi.org/10.1038/s41467-018-03663-5
  • Primary Citation of Related Structures:  
    6BKM, 6BKN, 6BKO, 6BKP, 6BKQ, 6BKR, 6BKS, 6BKT

  • PubMed Abstract: 

    The hemagglutinin (HA) receptor-binding site (RBS) in human influenza A viruses is critical for attachment to host cells, which imposes a functional constraint on its natural evolution. On the other hand, being part of the major antigenic sites, the HA RBS of human H3N2 viruses needs to constantly mutate to evade the immune system. From large-scale mutagenesis experiments, we here show that several of the natural RBS substitutions become integrated into an extensive epistatic network that prevents substitution reversion. X-ray structural analysis reveals the mechanistic consequences as well as changes in the mode of receptor binding. Further studies are necessary to elucidate whether such entrenchment limits future options for immune escape or adversely affect long-term viral fitness.


  • 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
A, C, E
323Influenza A virus (A/Hong Kong/1/1968(H3N2))Mutation(s): 1 
Gene Names: HA
UniProt
Find proteins for Q91MA7 (Influenza A virus (strain A/Hong Kong/1/1968 H3N2))
Explore Q91MA7 
Go to UniProtKB:  Q91MA7
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ91MA7
Sequence Annotations
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  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Hemagglutinin
B, D, F
174Influenza A virus (A/Hong Kong/1/1968(H3N2))Mutation(s): 0 
Gene Names: HA
UniProt
Find proteins for Q91MA7 (Influenza A virus (strain A/Hong Kong/1/1968 H3N2))
Explore Q91MA7 
Go to UniProtKB:  Q91MA7
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ91MA7
Sequence Annotations
Expand
  • Reference Sequence
Oligosaccharides

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Entity ID: 3
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
G, H
3N-Glycosylation
Glycosylation Resources
GlyTouCan:  G15407YE
GlyCosmos:  G15407YE
GlyGen:  G15407YE
Entity ID: 4
MoleculeChains Length2D Diagram Glycosylation3D Interactions
2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose
I, L, O
2N-Glycosylation
Glycosylation Resources
GlyTouCan:  G42666HT
GlyCosmos:  G42666HT
GlyGen:  G42666HT
Entity ID: 5
MoleculeChains Length2D Diagram Glycosylation3D Interactions
N-acetyl-alpha-neuraminic acid-(2-6)-beta-D-galactopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose
J, M
3N/A
Glycosylation Resources
GlyTouCan:  G73578JC
GlyCosmos:  G73578JC
GlyGen:  G73578JC
Entity ID: 6
MoleculeChains Length2D Diagram Glycosylation3D Interactions
alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose
K, N
5N-Glycosylation
Glycosylation Resources
GlyTouCan:  G22768VO
GlyCosmos:  G22768VO
GlyGen:  G22768VO
Entity ID: 7
MoleculeChains Length2D Diagram Glycosylation3D Interactions
N-acetyl-alpha-neuraminic acid-(2-6)-beta-D-galactopyranose
P
2N/A
Glycosylation Resources
GlyTouCan:  G63069TR
GlyCosmos:  G63069TR
GlyGen:  G63069TR
Biologically Interesting Molecules (External Reference) 1 Unique
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.25 Å
  • R-Value Free: 0.208 
  • R-Value Work: 0.178 
  • R-Value Observed: 0.179 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 208.784α = 90
b = 130.842β = 97.9
c = 72.179γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
HKL-2000data processing
HKL-2000data scaling
PHASERphasing

Structure Validation

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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: 2018-02-28
    Type: Initial release
  • Version 1.1: 2018-04-11
    Changes: Data collection, Database references
  • Version 1.2: 2019-12-11
    Changes: Author supporting evidence, Data collection
  • Version 2.0: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Advisory, 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