4JPK

Crystal structure of the germline-targeting HIV-1 gp120 engineered outer domain eOD-GT6 in complex with a putative VRC01 germline precursor Fab


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.40 Å
  • R-Value Free: 0.263 
  • R-Value Work: 0.200 
  • R-Value Observed: 0.203 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.4 of the entry. See complete history


Literature

Rational HIV immunogen design to target specific germline B cell receptors.

Jardine, J.Julien, J.P.Menis, S.Ota, T.Kalyuzhniy, O.McGuire, A.Sok, D.Huang, P.S.MacPherson, S.Jones, M.Nieusma, T.Mathison, J.Baker, D.Ward, A.B.Burton, D.R.Stamatatos, L.Nemazee, D.Wilson, I.A.Schief, W.R.

(2013) Science 340: 711-716

  • DOI: https://doi.org/10.1126/science.1234150
  • Primary Citation of Related Structures:  
    4JPI, 4JPJ, 4JPK

  • PubMed Abstract: 

    Vaccine development to induce broadly neutralizing antibodies (bNAbs) against HIV-1 is a global health priority. Potent VRC01-class bNAbs against the CD4 binding site of HIV gp120 have been isolated from HIV-1-infected individuals; however, such bNAbs have not been induced by vaccination. Wild-type gp120 proteins lack detectable affinity for predicted germline precursors of VRC01-class bNAbs, making them poor immunogens to prime a VRC01-class response. We employed computation-guided, in vitro screening to engineer a germline-targeting gp120 outer domain immunogen that binds to multiple VRC01-class bNAbs and germline precursors, and elucidated germline binding crystallographically. When multimerized on nanoparticles, this immunogen (eOD-GT6) activates germline and mature VRC01-class B cells. Thus, eOD-GT6 nanoparticles have promise as a vaccine prime. In principle, germline-targeting strategies could be applied to other epitopes and pathogens.


  • Organizational Affiliation

    Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Putative VRC01 germline precursor Fab heavy chainA [auth H]248Homo sapiensMutation(s): 0 
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Sequence Annotations
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  • Reference Sequence
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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Putative VRC01 germline precursor Fab light chainB [auth L]210Homo sapiensMutation(s): 0 
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Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
Sequence Annotations
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  • Reference Sequence
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Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
Germline-targeting HIV-1 gp120 engineered outer domain, eOD-GT6C [auth A]172Human immunodeficiency virus 1Mutation(s): 0 
UniProt
Find proteins for P04578 (Human immunodeficiency virus type 1 group M subtype B (isolate HXB2))
Explore P04578 
Go to UniProtKB:  P04578
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP04578
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
NAG
Query on NAG

Download Ideal Coordinates CCD File 
D [auth A],
E [auth A]
2-acetamido-2-deoxy-beta-D-glucopyranose
C8 H15 N O6
OVRNDRQMDRJTHS-FMDGEEDCSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.40 Å
  • R-Value Free: 0.263 
  • R-Value Work: 0.200 
  • R-Value Observed: 0.203 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 179.26α = 90
b = 63.3β = 90.43
c = 61.3γ = 90
Software Package:
Software NamePurpose
Blu-Icedata collection
PHASERphasing
PHENIXrefinement
XDSdata reduction
XDSdata scaling

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2013-04-10
    Type: Initial release
  • Version 1.1: 2013-05-22
    Changes: Database references
  • Version 1.2: 2014-01-15
    Changes: Source and taxonomy
  • Version 1.3: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Data collection, Derived calculations, Structure summary
  • Version 1.4: 2023-09-20
    Changes: Data collection, Database references, Refinement description, Structure summary