6A67

Crystal structure of influenza A virus H5 hemagglutinin globular head in complex with the Fab of antibody FLD21.140


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.33 Å
  • R-Value Free: 0.235 
  • R-Value Work: 0.197 
  • R-Value Observed: 0.199 

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This is version 1.4 of the entry. See complete history


Literature

Complementary recognition of the receptor-binding site of highly pathogenic H5N1 influenza viruses by two human neutralizing antibodies.

Zuo, Y.Wang, P.Sun, J.Guo, S.Wang, G.Zuo, T.Fan, S.Zhou, P.Liang, M.Shi, X.Wang, X.Zhang, L.

(2018) J Biol Chem 293: 16503-16517

  • DOI: https://doi.org/10.1074/jbc.RA118.004604
  • Primary Citation of Related Structures:  
    6A67

  • PubMed Abstract: 

    The highly pathogenic avian influenza virus H5N1 is a major threat to global public health and therefore a high-priority target of current vaccine development. The receptor-binding site (RBS) on the globular head of hemagglutinin (HA) in the viral envelope is one of the major target sites for antibody recognition against H5N1 and other influenza viruses. Here, we report the identification and characterization of a pair of human RBS-specific antibodies, designated FLD21.140 and AVFluIgG03, that are mutually complementary in their neutralizing activities against a diverse panel of H5N1 viruses. Crystallographic analysis and site-directed mutagenesis revealed that the two antibodies share a similar RBS-binding mode, and their individual specificities are governed by residues at positions 133a, 144, and 145. Specifically, FLD21.140 preferred Leu-133a/Lys-144/Ser-145, whereas AVFluIgG03 favored Ser-133a/Thr-144/Pro-145 residue triplets, both of which perfectly matched the most prevalent residues in viruses from epidemic-originating regions. Of note, according to an analysis of 3758 H5 HA sequences available in the Influenza Virus Database at the National Center for Biotechnology Information, the residues Leu-133a/Ser-133a and Ser-145/Pro-145 constituted more than 87.6 and 99.3% of all residues at these two positions, respectively. Taken together, our results provide a structural understanding for the neutralizing complementarity of these two antibodies and improve our understanding of the RBS-specific antibody response against H5N1 infection in humans.


  • Organizational Affiliation

    From the Comprehensive AIDS Research Center, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing 100084.


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
FLD21.140 Heavy ChainA [auth H],
C
226Homo sapiensMutation(s): 0 
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  • Reference Sequence
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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
FLD21.140 Light ChainB [auth L],
D
217Homo sapiensMutation(s): 0 
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Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
HemagglutininE [auth B],
F [auth A]
230Influenza A virus (A/Thailand/1(KAN-1)/2004(H5N1))Mutation(s): 0 
UniProt
Find proteins for Q6Q794 (Influenza A virus)
Explore Q6Q794 
Go to UniProtKB:  Q6Q794
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UniProt GroupQ6Q794
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.33 Å
  • R-Value Free: 0.235 
  • R-Value Work: 0.197 
  • R-Value Observed: 0.199 
  • Space Group: P 42 2 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 168.106α = 90
b = 168.106β = 90
c = 147.188γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
HKL-2000data reduction
HKL-2000data scaling
PHASERphasing

Structure Validation

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Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
National Natural Science Foundation of ChinaChina81530065
National Natural Science Foundation of ChinaChina81661128042
National Natural Science Foundation of ChinaChina31470751
National Natural Science Foundation of ChinaChinaU1405228
Ministry of Science and Technology (China)China2016YFD0500307
Ministry of Science and Technology (China)China2012ZX10001-004
Ministry of Science and Technology (China)China2012ZX10001-006
Ministry of Science and Technology (China)China2012ZX10001-009
Ministry of Science and Technology (China)China2017ZX10201-101
Ministry of Science and Technology (China)China2014CB542500-03

Revision History  (Full details and data files)

  • Version 1.0: 2018-08-29
    Type: Initial release
  • Version 1.1: 2018-09-19
    Changes: Data collection, Database references
  • Version 1.2: 2018-11-21
    Changes: Data collection, Database references
  • Version 1.3: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Data collection, Derived calculations, Structure summary
  • Version 1.4: 2023-11-22
    Changes: Data collection, Database references, Refinement description, Structure summary