5W42

Crystal structure of human monoclonal antibody H3v-47 in complex with influenza virus hemagglutinin from A/Minnesota/11/2010 (H3N2)


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.57 Å
  • R-Value Free: 0.228 
  • R-Value Work: 0.196 
  • R-Value Observed: 0.198 

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Literature

A multifunctional human monoclonal neutralizing antibody that targets a unique conserved epitope on influenza HA.

Bangaru, S.Zhang, H.Gilchuk, I.M.Voss, T.G.Irving, R.P.Gilchuk, P.Matta, P.Zhu, X.Lang, S.Nieusma, T.Richt, J.A.Albrecht, R.A.Vanderven, H.A.Bombardi, R.Kent, S.J.Ward, A.B.Wilson, I.A.Crowe, J.E.

(2018) Nat Commun 9: 2669-2669

  • DOI: https://doi.org/10.1038/s41467-018-04704-9
  • Primary Citation of Related Structures:  
    5W42, 5XRQ, 5XRS, 5XRT

  • PubMed Abstract: 

    The high rate of antigenic drift in seasonal influenza viruses necessitates frequent changes in vaccine composition. Recent seasonal H3 vaccines do not protect against swine-origin H3N2 variant (H3N2v) strains that recently have caused severe human infections. Here, we report a human V H 1-69 gene-encoded monoclonal antibody (mAb) designated H3v-47 that exhibits potent cross-reactive neutralization activity against human and swine H3N2 viruses that circulated since 1989. The crystal structure and electron microscopy reconstruction of H3v-47 Fab with the H3N2v hemagglutinin (HA) identify a unique epitope spanning the vestigial esterase and receptor-binding subdomains that is distinct from that of any known neutralizing antibody for influenza A H3 viruses. MAb H3v-47 functions largely by blocking viral egress from infected cells. Interestingly, H3v-47 also engages Fcγ receptor and mediates antibody dependent cellular cytotoxicity (ADCC). This newly identified conserved epitope can be used in design of novel immunogens for development of broadly protective H3 vaccines.


  • Organizational Affiliation

    Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, 37232, USA.


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Hemagglutinin329Influenza A virus (A/swine/Minnesota/A01134337/2010(H3N2))Mutation(s): 0 
Gene Names: HA
UniProt
Find proteins for I0AXC3 (Influenza A virus)
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Go to UniProtKB:  I0AXC3
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupI0AXC3
Sequence Annotations
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  • Reference Sequence
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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Hemagglutinin174Influenza A virus (A/swine/Minnesota/A01134337/2010(H3N2))Mutation(s): 0 
Gene Names: HA
UniProt
Find proteins for I0AXC3 (Influenza A virus)
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Go to UniProtKB:  I0AXC3
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupI0AXC3
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  • Reference Sequence
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Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
Fab H3v-47 heavy chainC [auth H]236Homo sapiensMutation(s): 0 
UniProt
Find proteins for Q6N089 (Homo sapiens)
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Go to UniProtKB:  Q6N089
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UniProt GroupQ6N089
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  • Reference Sequence
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Entity ID: 4
MoleculeChains Sequence LengthOrganismDetailsImage
Fab H3v-47 light chainD [auth L]214Homo sapiensMutation(s): 0 
UniProt
Find proteins for Q8TCD0 (Homo sapiens)
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Go to UniProtKB:  Q8TCD0
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UniProt GroupQ8TCD0
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  • Reference Sequence
Oligosaccharides

Help

Entity ID: 5
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-glucopyranoseE [auth C],
I [auth G]
5N-Glycosylation
Glycosylation Resources
GlyTouCan:  G22768VO
GlyCosmos:  G22768VO
GlyGen:  G22768VO
Entity ID: 6
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-glucopyranoseF [auth D]4N-Glycosylation
Glycosylation Resources
GlyTouCan:  G81315DD
GlyCosmos:  G81315DD
GlyGen:  G81315DD
Entity ID: 7
MoleculeChains Length2D Diagram Glycosylation3D Interactions
alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]alpha-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranoseG [auth E]6N-Glycosylation
Glycosylation Resources
GlyTouCan:  G36544AC
GlyCosmos:  G36544AC
GlyGen:  G36544AC
Entity ID: 8
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-glucopyranoseH [auth F]3N/A
Glycosylation Resources
GlyTouCan:  G15407YE
GlyCosmos:  G15407YE
GlyGen:  G15407YE
Entity ID: 9
MoleculeChains Length2D Diagram Glycosylation3D Interactions
2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranoseJ [auth I]2N-Glycosylation
Glycosylation Resources
GlyTouCan:  G42666HT
GlyCosmos:  G42666HT
GlyGen:  G42666HT
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.57 Å
  • R-Value Free: 0.228 
  • R-Value Work: 0.196 
  • R-Value Observed: 0.198 
  • Space Group: P 21 3
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 194.622α = 90
b = 194.622β = 90
c = 194.622γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
HKL-2000data reduction
HKL-2000data 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 StatesU19 AI117905

Revision History  (Full details and data files)

  • Version 1.0: 2018-07-25
    Type: Initial release
  • Version 1.1: 2019-12-11
    Changes: Author supporting evidence
  • 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