4JAN

crystal structure of broadly neutralizing antibody CH103 in complex with HIV-1 gp120


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.15 Å
  • R-Value Free: 0.256 
  • R-Value Work: 0.196 
  • R-Value Observed: 0.199 

Starting Model: experimental
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Ligand Structure Quality Assessment 


This is version 1.7 of the entry. See complete history


Literature

Co-evolution of a broadly neutralizing HIV-1 antibody and founder virus.

Liao, H.X.Lynch, R.Zhou, T.Gao, F.Alam, S.M.Boyd, S.D.Fire, A.Z.Roskin, K.M.Schramm, C.A.Zhang, Z.Zhu, J.Shapiro, L.Mullikin, J.C.Gnanakaran, S.Hraber, P.Wiehe, K.Kelsoe, G.Yang, G.Xia, S.M.Montefiori, D.C.Parks, R.Lloyd, K.E.Scearce, R.M.Soderberg, K.A.Cohen, M.Kamanga, G.Louder, M.K.Tran, L.M.Chen, Y.Cai, F.Chen, S.Moquin, S.Du, X.Joyce, M.G.Srivatsan, S.Zhang, B.Zheng, A.Shaw, G.M.Hahn, B.H.Kepler, T.B.Korber, B.T.Kwong, P.D.Mascola, J.R.Haynes, B.F.

(2013) Nature 496: 469-476

  • DOI: https://doi.org/10.1038/nature12053
  • Primary Citation of Related Structures:  
    4JAM, 4JAN

  • PubMed Abstract: 

    Current human immunodeficiency virus-1 (HIV-1) vaccines elicit strain-specific neutralizing antibodies. However, cross-reactive neutralizing antibodies arise in approximately 20% of HIV-1-infected individuals, and details of their generation could provide a blueprint for effective vaccination. Here we report the isolation, evolution and structure of a broadly neutralizing antibody from an African donor followed from the time of infection. The mature antibody, CH103, neutralized approximately 55% of HIV-1 isolates, and its co-crystal structure with the HIV-1 envelope protein gp120 revealed a new loop-based mechanism of CD4-binding-site recognition. Virus and antibody gene sequencing revealed concomitant virus evolution and antibody maturation. Notably, the unmutated common ancestor of the CH103 lineage avidly bound the transmitted/founder HIV-1 envelope glycoprotein, and evolution of antibody neutralization breadth was preceded by extensive viral diversification in and near the CH103 epitope. These data determine the viral and antibody evolution leading to induction of a lineage of HIV-1 broadly neutralizing antibodies, and provide insights into strategies to elicit similar antibodies by vaccination.


  • Organizational Affiliation

    Duke University Human Vaccine Institute, Departments of Medicine and Immunology, Duke University School of Medicine, Durham, North Carolina 27710, USA. [email protected]


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
ENVELOPE GLYCOPROTEIN GP120 of HIV-1 clade CA [auth G],
D [auth I]
355Human immunodeficiency virus 1Mutation(s): 0 
UniProt
Find proteins for R4GRV3 (Human immunodeficiency virus 1)
Explore R4GRV3 
Go to UniProtKB:  R4GRV3
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupR4GRV3
Glycosylation
Glycosylation Sites: 5
Sequence Annotations
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  • Reference Sequence
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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
ANTIGEN BINDING FRAGMENT OF HEAVY CHAIN of CH103B [auth H],
E [auth A]
226Homo sapiensMutation(s): 0 
Entity Groups  
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Sequence Annotations
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  • Reference Sequence
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Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
ANTIGEN BINDING FRAGMENT OF LIGHT CHAIN of CH103C [auth L],
F [auth B]
209Homo sapiensMutation(s): 0 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
NAG
Query on NAG

Download Ideal Coordinates CCD File 
G
H [auth G]
I [auth G]
J [auth G]
K [auth G]
G,
H [auth G],
I [auth G],
J [auth G],
K [auth G],
O [auth I],
P [auth I],
Q [auth I],
R [auth I],
S [auth I]
2-acetamido-2-deoxy-beta-D-glucopyranose
C8 H15 N O6
OVRNDRQMDRJTHS-FMDGEEDCSA-N
GOL
Query on GOL

Download Ideal Coordinates CCD File 
N [auth L],
T [auth B]
GLYCEROL
C3 H8 O3
PEDCQBHIVMGVHV-UHFFFAOYSA-N
NA
Query on NA

Download Ideal Coordinates CCD File 
L [auth H],
M [auth L]
SODIUM ION
Na
FKNQFGJONOIPTF-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.15 Å
  • R-Value Free: 0.256 
  • R-Value Work: 0.196 
  • R-Value Observed: 0.199 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 48.943α = 90
b = 208.651β = 107.21
c = 69.422γ = 90
Software Package:
Software NamePurpose
SERGUIdata 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: 2013-04-03
    Type: Initial release
  • Version 1.1: 2013-04-17
    Changes: Database references
  • Version 1.2: 2013-05-01
    Changes: Database references
  • Version 1.3: 2013-05-29
    Changes: Database references
  • Version 1.4: 2014-07-16
    Changes: Other
  • Version 1.5: 2019-01-09
    Changes: Data collection, Derived calculations
  • Version 1.6: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Data collection, Derived calculations, Structure summary
  • Version 1.7: 2023-09-20
    Changes: Data collection, Database references, Refinement description, Structure summary