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 5VOC

Crystal structure of HCMV Pentamer in complex with neutralizing antibody 8I21 - Low resolution dataset for initial phasing by SAD


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.99 Å
  • R-Value Free: 0.276 
  • R-Value Work: 0.259 
  • R-Value Observed: 0.260 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 2.1 of the entry. See complete history


Literature

Structural basis for potent antibody-mediated neutralization of human cytomegalovirus.

Chandramouli, S.Malito, E.Nguyen, T.Luisi, K.Donnarumma, D.Xing, Y.Norais, N.Yu, D.Carfi, A.

(2017) Sci Immunol 2

  • DOI: https://doi.org/10.1126/sciimmunol.aan1457
  • Primary Citation of Related Structures:  
    5VOB, 5VOC, 5VOD

  • PubMed Abstract: 

    Human cytomegalovirus (HCMV) is the leading viral cause of birth defects and organ transplant rejection. The HCMV gH/gL/UL128/UL130/UL131A complex (Pentamer) is the main target of humoral responses and thus a key vaccine candidate. We report two structures of Pentamer bound to human neutralizing antibodies, 8I21 and 9I6, at 3.0 and 5.9 Å resolution, respectively. The HCMV gH/gL architecture is similar to that of Epstein-Barr virus (EBV) except for amino-terminal extensions on both subunits. The extension of gL forms a subdomain composed of a three-helix bundle and a β hairpin that acts as a docking site for UL128/UL130/UL131A. Structural analysis reveals that Pentamer is a flexible molecule, and suggests sites for engineering stabilizing mutations. We also identify immunogenic surfaces important for cellular interactions by epitope mapping and functional assays. These results can guide the development of effective vaccines and immunotherapeutics against HCMV.


  • Organizational Affiliation

    GSK Vaccines, 14200 Shady Grove Road, Rockville, MD 20850, USA.


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Envelope glycoprotein H725Human herpesvirus 5 strain MerlinMutation(s): 0 
Gene Names: gHUL75
UniProt
Find proteins for Q6SW67 (Human cytomegalovirus (strain Merlin))
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Go to UniProtKB:  Q6SW67
Entity Groups  
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UniProt GroupQ6SW67
Glycosylation
Glycosylation Sites: 3
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  • Reference Sequence
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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Envelope glycoprotein L278Human herpesvirus 5 strain 5508Mutation(s): 0 
Gene Names: gLUL115
UniProt
Find proteins for Q68674 (Human cytomegalovirus (strain 5508))
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Go to UniProtKB:  Q68674
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UniProt GroupQ68674
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Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
Envelope glycoprotein UL128171Human herpesvirus 5 strain AD169Mutation(s): 0 
Gene Names: UL128
UniProt
Find proteins for P16837 (Human cytomegalovirus (strain AD169))
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Go to UniProtKB:  P16837
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UniProt GroupP16837
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Entity ID: 4
MoleculeChains Sequence LengthOrganismDetailsImage
Envelope glycoprotein UL130252Human herpesvirus 5 strain MerlinMutation(s): 0 
Gene Names: UL130
UniProt
Find proteins for F5HCP3 (Human cytomegalovirus (strain Merlin))
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Go to UniProtKB:  F5HCP3
Entity Groups  
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UniProt GroupF5HCP3
Glycosylation
Glycosylation Sites: 2
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Entity ID: 5
MoleculeChains Sequence LengthOrganismDetailsImage
Envelope glycoprotein UL131A129Human herpesvirus 5 strain MerlinMutation(s): 0 
Gene Names: UL131A
UniProt
Find proteins for F5HET4 (Human cytomegalovirus (strain Merlin))
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UniProt GroupF5HET4
Glycosylation
Glycosylation Sites: 1
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Entity ID: 6
MoleculeChains Sequence LengthOrganismDetailsImage
Fab 8I21 heavy chainF [auth H]289Homo sapiensMutation(s): 0 
UniProt
Find proteins for S6B291 (Homo sapiens)
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UniProt GroupS6B291
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Entity ID: 7
MoleculeChains Sequence LengthOrganismDetailsImage
Fab 8I21 light chainG [auth L]235Homo sapiensMutation(s): 0 
Gene Names: IGKV3-15
UniProt
Find proteins for Q6GMX0 (Homo sapiens)
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UniProt GroupQ6GMX0
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Oligosaccharides

Help

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-Glycosylation
Glycosylation Resources
GlyTouCan:  G15407YE
GlyCosmos:  G15407YE
GlyGen:  G15407YE
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.99 Å
  • R-Value Free: 0.276 
  • R-Value Work: 0.259 
  • R-Value Observed: 0.260 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 124.415α = 90
b = 146.532β = 90
c = 190.947γ = 90
Software Package:
Software NamePurpose
BUSTERrefinement
XDSdata reduction
XSCALEdata scaling
PHENIXphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2017-07-05
    Type: Initial release
  • Version 1.1: 2017-07-12
    Changes: Database references
  • Version 1.2: 2017-08-23
    Changes: Database references
  • Version 2.0: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Atomic model, Data collection, Derived calculations, Structure summary
  • Version 2.1: 2024-10-16
    Changes: Data collection, Database references, Structure summary