4JPV

Crystal structure of broadly and potently neutralizing antibody 3bnc117 in complex with hiv-1 gp120


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.83 Å
  • R-Value Free: 0.259 
  • R-Value Work: 0.199 
  • R-Value Observed: 0.203 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

Somatic Mutations of the Immunoglobulin Framework Are Generally Required for Broad and Potent HIV-1 Neutralization.

Klein, F.Diskin, R.Scheid, J.F.Gaebler, C.Mouquet, H.Georgiev, I.S.Pancera, M.Zhou, T.Incesu, R.B.Fu, B.Z.Gnanapragasam, P.N.Oliveira, T.Y.Seaman, M.S.Kwong, P.D.Bjorkman, P.J.Nussenzweig, M.C.

(2013) Cell 153: 126-138

  • DOI: https://doi.org/10.1016/j.cell.2013.03.018
  • Primary Citation of Related Structures:  
    4GW4, 4JPV, 4JPW

  • PubMed Abstract: 

    Broadly neutralizing antibodies (bNAbs) to HIV-1 can prevent infection and are therefore of great importance for HIV-1 vaccine design. Notably, bNAbs are highly somatically mutated and generated by a fraction of HIV-1-infected individuals several years after infection. Antibodies typically accumulate mutations in the complementarity determining region (CDR) loops, which usually contact the antigen. The CDR loops are scaffolded by canonical framework regions (FWRs) that are both resistant to and less tolerant of mutations. Here, we report that in contrast to most antibodies, including those with limited HIV-1 neutralizing activity, most bNAbs require somatic mutations in their FWRs. Structural and functional analyses reveal that somatic mutations in FWR residues enhance breadth and potency by providing increased flexibility and/or direct antigen contact. Thus, in bNAbs, FWRs play an essential role beyond scaffolding the CDR loops and their unusual contribution to potency and breadth should be considered in HIV-1 vaccine design.


  • Organizational Affiliation

    Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
HIV-1 CLADE A STRAIN 93TH057 GP120 WITH LOOP d AND LOOPD V5 REPLACED FROM HIV STRAIN 3415V1A [auth G]352Human immunodeficiency virus 1Mutation(s): 0 
UniProt
Find proteins for Q0ED31 (Human immunodeficiency virus 1)
Explore Q0ED31 
Go to UniProtKB:  Q0ED31
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ0ED31
Sequence Annotations
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  • Reference Sequence
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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
HEAVY CHAIN OF ANTIBODY 3BNC117B [auth H]226Homo sapiensMutation(s): 0 
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  • Reference Sequence
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Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
LIGHT CHAIN OF ANTIBODY 3BNC117C [auth L]206Homo sapiensMutation(s): 0 
Entity Groups  
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Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
EPE
Query on EPE

Download Ideal Coordinates CCD File 
N [auth G]4-(2-HYDROXYETHYL)-1-PIPERAZINE ETHANESULFONIC ACID
C8 H18 N2 O4 S
JKMHFZQWWAIEOD-UHFFFAOYSA-N
NAG
Query on NAG

Download Ideal Coordinates CCD File 
D [auth G]
E [auth G]
F [auth G]
G
H [auth G]
D [auth G],
E [auth G],
F [auth G],
G,
H [auth G],
I [auth G],
J [auth G],
K [auth G],
L [auth G],
M [auth G],
R [auth L]
2-acetamido-2-deoxy-beta-D-glucopyranose
C8 H15 N O6
OVRNDRQMDRJTHS-FMDGEEDCSA-N
EDO
Query on EDO

Download Ideal Coordinates CCD File 
O [auth G],
P [auth G],
Q [auth G],
S [auth L]
1,2-ETHANEDIOL
C2 H6 O2
LYCAIKOWRPUZTN-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.83 Å
  • R-Value Free: 0.259 
  • R-Value Work: 0.199 
  • R-Value Observed: 0.203 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 68.627α = 90
b = 69.887β = 90
c = 231.633γ = 90
Software Package:
Software NamePurpose
HKL-2000data collection
PHASERphasing
PHENIXrefinement
HKL-2000data reduction
HKL-2000data 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: 2013-04-17
    Type: Initial release
  • Version 1.1: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Data collection, Derived calculations, Structure summary
  • Version 1.2: 2021-06-02
    Changes: Source and taxonomy, Structure summary
  • Version 1.3: 2023-09-20
    Changes: Data collection, Database references, Refinement description