5KUY

Influenza hemagglutinin H3 A/Hong Kong/1/1968 in complex with designed inhibitor protein HSB.2A


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.60 Å
  • R-Value Free: 0.204 
  • R-Value Work: 0.173 
  • R-Value Observed: 0.174 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 2.1 of the entry. See complete history


Literature

Computational design of trimeric influenza-neutralizing proteins targeting the hemagglutinin receptor binding site.

Strauch, E.M.Bernard, S.M.La, D.Bohn, A.J.Lee, P.S.Anderson, C.E.Nieusma, T.Holstein, C.A.Garcia, N.K.Hooper, K.A.Ravichandran, R.Nelson, J.W.Sheffler, W.Bloom, J.D.Lee, K.K.Ward, A.B.Yager, P.Fuller, D.H.Wilson, I.A.Baker, D.

(2017) Nat Biotechnol 35: 667-671

  • DOI: https://doi.org/10.1038/nbt.3907
  • Primary Citation of Related Structures:  
    5KUX, 5KUY

  • PubMed Abstract: 

    Many viral surface glycoproteins and cell surface receptors are homo-oligomers, and thus can potentially be targeted by geometrically matched homo-oligomers that engage all subunits simultaneously to attain high avidity and/or lock subunits together. The adaptive immune system cannot generally employ this strategy since the individual antibody binding sites are not arranged with appropriate geometry to simultaneously engage multiple sites in a single target homo-oligomer. We describe a general strategy for the computational design of homo-oligomeric protein assemblies with binding functionality precisely matched to homo-oligomeric target sites. In the first step, a small protein is designed that binds a single site on the target. In the second step, the designed protein is assembled into a homo-oligomer such that the designed binding sites are aligned with the target sites. We use this approach to design high-avidity trimeric proteins that bind influenza A hemagglutinin (HA) at its conserved receptor binding site. The designed trimers can both capture and detect HA in a paper-based diagnostic format, neutralizes influenza in cell culture, and completely protects mice when given as a single dose 24 h before or after challenge with influenza.


  • Organizational Affiliation

    Department of Biochemistry, University of Washington, Seattle, Washington, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Hemagglutinin HA1
A, C, E
323Influenza 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
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  • Reference Sequence
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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Hemagglutinin HA2
B, D, F
177Influenza 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
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Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
Designed influenza inhibitor HSB.2A
G, H, I
97synthetic constructMutation(s): 0 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
Sequence Annotations
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  • Reference Sequence
Oligosaccharides

Help

Entity ID: 4
MoleculeChains Length2D Diagram Glycosylation3D Interactions
2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose
J, K, L, M, O
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
N
3N-Glycosylation
Glycosylation Resources
GlyTouCan:  G15407YE
GlyCosmos:  G15407YE
GlyGen:  G15407YE
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.60 Å
  • R-Value Free: 0.204 
  • R-Value Work: 0.173 
  • R-Value Observed: 0.174 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 154.259α = 90
b = 219.322β = 117.78
c = 104.524γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
HKL-2000data reduction
SCALAdata 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

Revision History  (Full details and data files)

  • Version 1.0: 2017-06-14
    Type: Initial release
  • Version 1.1: 2017-06-28
    Changes: Database references
  • Version 1.2: 2017-07-26
    Changes: Author supporting evidence, Database references
  • Version 1.3: 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, Refinement description, Structure summary