6AJ9

The structure of Enterovirus D68 mature virion in complex with Fab 15C5 and 11G1

  • Classification: VIRUS
  • Organism(s): Mus musculus, enterovirus D68
  • Mutation(s): No 

  • Deposited: 2018-08-27 Released: 2018-11-07 
  • Deposition Author(s): Zheng, Q.B., Zhu, R., Xu, L.F., He, M.Z., Yan, X.D., Cheng, T., Li, S.W.
  • Funding Organization(s): National Natural Science Foundation of China, National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS), National Institutes of Health/National Institute of Dental and Craniofacial Research (NIH/NIDCR), National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID), National Institutes of Health/National Center for Research Resources (NIH/NCRR), National Science Foundation (United States)

Experimental Data Snapshot

  • Method: ELECTRON MICROSCOPY
  • Resolution: 3.50 Å
  • Aggregation State: PARTICLE 
  • Reconstruction Method: SINGLE PARTICLE 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Atomic structures of enterovirus D68 in complex with two monoclonal antibodies define distinct mechanisms of viral neutralization

Zheng, Q.Zhu, R.Xu, L.He, M.Yan, X.Liu, D.Yin, Z.Wu, Y.Li, Y.Yang, L.Hou, W.Li, S.Li, Z.Chen, Z.Li, Z.Yu, H.Gu, Y.Zhang, J.Baker, T.S.Zhou, Z.H.Graham, B.S.Cheng, T.Li, S.Xia, N.

(2019) Nat Microbiol 4: 124-133

  • DOI: https://doi.org/10.1038/s41564-018-0275-7
  • Primary Citation of Related Structures:  
    6AJ0, 6AJ2, 6AJ3, 6AJ7, 6AJ9

  • PubMed Abstract: 

    Enterovirus D68 (EV-D68) undergoes structural transformation between mature, cell-entry intermediate (A-particle) and empty forms throughout its life cycle. Structural information for the various forms and antibody-bound capsids will facilitate the development of effective vaccines and therapeutics against EV-D68 infection, which causes childhood respiratory and paralytic diseases worldwide. Here, we report the structures of three EV-D68 capsid states representing the virus at major phases. We further describe two original monoclonal antibodies (15C5 and 11G1) with distinct structurally defined mechanisms for virus neutralization. 15C5 and 11G1 engage the capsid loci at icosahedral three-fold and five-fold axes, respectively. To block viral attachment, 15C5 binds three forms of capsids, and triggers mature virions to transform into A-particles, mimicking engagement by the functional receptor ICAM-5, whereas 11G1 exclusively recognizes the A-particle. Our data provide a structural and molecular explanation for the transition of picornavirus capsid conformations and demonstrate distinct mechanisms for antibody-mediated neutralization.


  • Organizational Affiliation

    State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Science, School of Public Health, Xiamen University, Xiamen, China.


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
VL of Fab 11G1A [auth E]113Mus musculusMutation(s): 0 
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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
VH of Fab 11G1B [auth D]122Mus musculusMutation(s): 0 
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Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
VL of Fab 15C5C [auth L]107Mus musculusMutation(s): 0 
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Entity ID: 4
MoleculeChains Sequence LengthOrganismDetailsImage
VH of Fab 15C5D [auth H]116Mus musculusMutation(s): 0 
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Entity ID: 5
MoleculeChains Sequence LengthOrganismDetailsImage
Capsid protein VP1E [auth A]295enterovirus D68Mutation(s): 0 
UniProt
Find proteins for A0A097F8Q2 (Human enterovirus D68)
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UniProt GroupA0A097F8Q2
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Entity ID: 6
MoleculeChains Sequence LengthOrganismDetailsImage
Capsid protein VP2F [auth B]248enterovirus D68Mutation(s): 0 
UniProt
Find proteins for A0A097F8Q2 (Human enterovirus D68)
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Entity ID: 7
MoleculeChains Sequence LengthOrganismDetailsImage
Capsid protein VP3G [auth C]247enterovirus D68Mutation(s): 0 
UniProt
Find proteins for A0A097F8Q2 (Human enterovirus D68)
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Go to UniProtKB:  A0A097F8Q2
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UniProt GroupA0A097F8Q2
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Experimental Data & Validation

Experimental Data

  • Method: ELECTRON MICROSCOPY
  • Resolution: 3.50 Å
  • Aggregation State: PARTICLE 
  • Reconstruction Method: SINGLE PARTICLE 
EM Software:
TaskSoftware PackageVersion
RECONSTRUCTIONRELION2.0

Structure Validation

View Full Validation Report



Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
National Natural Science Foundation of ChinaChina81401669
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)United StatesR37-GM33050
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)United StatesGM071940
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)United States1U24GM116792
National Institutes of Health/National Institute of Dental and Craniofacial Research (NIH/NIDCR)United StatesDE025567
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)United StatesAI094386
National Institutes of Health/National Center for Research Resources (NIH/NCRR)United States1S10RR23057
National Science Foundation (United States)United StatesDBI-1338135
National Science Foundation (United States)United StatesDMR-1548924
National Science Foundation (United States)United StatesDBI-1338135
National Science Foundation (United States)United StatesDMR-1548924

Revision History  (Full details and data files)

  • Version 1.0: 2018-11-07
    Type: Initial release
  • Version 1.1: 2018-11-21
    Changes: Data collection, Database references
  • Version 1.2: 2018-12-26
    Changes: Data collection, Database references
  • Version 1.3: 2022-03-23
    Changes: Author supporting evidence, Database references, Derived calculations