4UBD

Crystal structure of a neutralizing human monoclonal antibody with 1968 H3 HA


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.50 Å
  • R-Value Free: 0.258 
  • R-Value Work: 0.212 
  • R-Value Observed: 0.215 

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Ligand Structure Quality Assessment 


This is version 2.1 of the entry. See complete history


Literature

A potent broad-spectrum protective human monoclonal antibody crosslinking two haemagglutinin monomers of influenza A virus.

Wu, Y.Cho, M.Shore, D.Song, M.Choi, J.Jiang, T.Deng, Y.Q.Bourgeois, M.Almli, L.Yang, H.Chen, L.M.Shi, Y.Qi, J.Li, A.Yi, K.S.Chang, M.Bae, J.S.Lee, H.Shin, J.Stevens, J.Hong, S.Qin, C.F.Gao, G.F.Chang, S.J.Donis, R.O.

(2015) Nat Commun 6: 7708-7708

  • DOI: https://doi.org/10.1038/ncomms8708
  • Primary Citation of Related Structures:  
    4R8W, 4UBD

  • PubMed Abstract: 

    Effective annual influenza vaccination requires frequent changes in vaccine composition due to both antigenic shift for different subtype hemagglutinins (HAs) and antigenic drift in a particular HA. Here we present a broadly neutralizing human monoclonal antibody with an unusual binding modality. The antibody, designated CT149, was isolated from convalescent patients infected with pandemic H1N1 in 2009. CT149 is found to neutralize all tested group 2 and some group 1 influenza A viruses by inhibiting low pH-induced, HA-mediated membrane fusion. It promotes killing of infected cells by Fc-mediated antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity. X-ray crystallographic data reveal that CT149 binds primarily to the fusion domain in HA2, and the light chain is also largely involved in binding. The epitope recognized by this antibody comprises amino-acid residues from two adjacent protomers of HA. This binding characteristic of CT149 will provide more information to support the design of more potent influenza vaccines.


  • Organizational Affiliation

    1] CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, No. 1 West Beichen Road, Beijing 100101, China. [2] Center for Influenza Research and Early-warning, Chinese Academy of Sciences, No. 1 West Beichen Road, Beijing 100101, China.


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Hemagglutinin HA1 chain321Influenza 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 chain175Influenza 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
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  • Reference Sequence
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Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
monoclonal antibody H chain226Homo sapiensMutation(s): 0 
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Entity ID: 4
MoleculeChains Sequence LengthOrganismDetailsImage
monoclonal antibody L chain215Homo sapiensMutation(s): 0 
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  • Reference Sequence
Oligosaccharides

Help

Entity ID: 5
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
BA [auth b],
CA [auth c],
DA [auth d],
EA [auth e],
GA [auth g],
BA [auth b],
CA [auth c],
DA [auth d],
EA [auth e],
GA [auth g],
Y [auth W]
4N-Glycosylation
Glycosylation Resources
GlyTouCan:  G81315DD
GlyCosmos:  G81315DD
GlyGen:  G81315DD
Entity ID: 6
MoleculeChains Length2D Diagram Glycosylation3D Interactions
2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranoseAA [auth a],
FA [auth f],
Z
2N-Glycosylation
Glycosylation Resources
GlyTouCan:  G42666HT
GlyCosmos:  G42666HT
GlyGen:  G42666HT
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.50 Å
  • R-Value Free: 0.258 
  • R-Value Work: 0.212 
  • R-Value Observed: 0.215 
  • Space Group: P 31
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 128.7α = 90
b = 128.7β = 90
c = 428.319γ = 120
Software Package:
Software NamePurpose
REFMACrefinement

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2015-06-24
    Type: Initial release
  • Version 1.1: 2015-08-05
    Changes: Database references
  • Version 1.2: 2017-09-27
    Changes: Data collection, Derived calculations
  • Version 1.3: 2020-03-04
    Changes: Data collection, Derived calculations
  • Version 2.0: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Advisory, Atomic model, Data collection, Derived calculations, Structure summary
  • Version 2.1: 2023-12-27
    Changes: Data collection, Database references, Refinement description, Structure summary