3LG7

Crystal structure of HIV epitope-scaffold 4E10_S0_1EZ3A_002_C


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.50 Å
  • R-Value Free: 0.301 
  • R-Value Work: 0.257 
  • R-Value Observed: 0.259 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

Computational Design of Epitope-Scaffolds Allows Induction of Antibodies Specific for a Poorly Immunogenic HIV Vaccine Epitope.

Correia, B.E.Ban, Y.E.Holmes, M.A.Xu, H.Ellingson, K.Kraft, Z.Carrico, C.Boni, E.Sather, D.N.Zenobia, C.Burke, K.Y.Bradley-Hewitt, T.Bruhn-Johannsen, J.F.Kalyuzhniy, O.Baker, D.Strong, R.K.Stamatatos, L.Schief, W.R.

(2010) Structure 18: 1116-1126

  • DOI: https://doi.org/10.1016/j.str.2010.06.010
  • Primary Citation of Related Structures:  
    3LEF, 3LF6, 3LF9, 3LG7, 3LH2, 3LHP

  • PubMed Abstract: 

    Broadly cross-reactive monoclonal antibodies define epitopes for vaccine development against HIV and other highly mutable viruses. Crystal structures are available for several such antibody-epitope complexes, but methods are needed to translate that structural information into immunogens that re-elicit similar antibodies. We describe a general computational method to design epitope-scaffolds in which contiguous structural epitopes are transplanted to scaffold proteins for conformational stabilization and immune presentation. Epitope-scaffolds designed for the poorly immunogenic but conserved HIV epitope 4E10 exhibited high epitope structural mimicry, bound with higher affinities to monoclonal antibody (mAb) 4E10 than the cognate peptide, and inhibited HIV neutralization by HIV+ sera. Rabbit immunization with an epitope-scaffold induced antibodies with structural specificity highly similar to mAb 4E10, an important advance toward elicitation of neutralizing activity. The results demonstrate that computationally designed epitope-scaffolds are valuable as structure-specific serological reagents and as immunogens to elicit antibodies with predetermined structural specificity.


  • Organizational Affiliation

    Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
4E10_S0_1EZ3A_002_C (T246)
A, B, C
133synthetic constructMutation(s): 0 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
SO4
Query on SO4

Download Ideal Coordinates CCD File 
D [auth A]
E [auth A]
F [auth A]
G [auth A]
H [auth B]
D [auth A],
E [auth A],
F [auth A],
G [auth A],
H [auth B],
I [auth B],
J [auth B],
K [auth B],
L [auth C],
M [auth C],
N [auth C]
SULFATE ION
O4 S
QAOWNCQODCNURD-UHFFFAOYSA-L
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
FME
Query on FME
A, B, C
L-PEPTIDE LINKINGC6 H11 N O3 SMET
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.50 Å
  • R-Value Free: 0.301 
  • R-Value Work: 0.257 
  • R-Value Observed: 0.259 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 91.6α = 90
b = 94.87β = 90
c = 108.39γ = 90
Software Package:
Software NamePurpose
CrystalCleardata collection
PHASERphasing
REFMACrefinement
CrystalCleardata reduction
CrystalCleardata scaling

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

  • Released Date: 2010-09-22 
  • Deposition Author(s): Holmes, M.A.

Revision History  (Full details and data files)

  • Version 1.0: 2010-09-22
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2023-09-06
    Changes: Data collection, Database references, Derived calculations, Refinement description