4RX4

Crystal structure of VH1-46 germline-derived CD4-binding site-directed antibody 8ANC134 in complex with HIV-1 clade A Q842.d12 gp120

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.45 Å
  • R-Value Free: 0.253 
  • R-Value Work: 0.208 
  • R-Value Observed: 0.210 

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Literature

Structural Repertoire of HIV-1-Neutralizing Antibodies Targeting the CD4 Supersite in 14 Donors.

Zhou, T., Lynch, R.M., Chen, L., Acharya, P., Wu, X., Doria-Rose, N.A., Joyce, M.G., Lingwood, D., Soto, C., Bailer, R.T., Ernandes, M.J., Kong, R., Longo, N.S., Louder, M.K., McKee, K., O'Dell, S., Schmidt, S.D., Tran, L., Yang, Z., Druz, A., Luongo, T.S., Moquin, S., Srivatsan, S., Yang, Y., Zhang, B., Zheng, A., Pancera, M., Kirys, T., Georgiev, I.S., Gindin, T., Peng, H.P., Yang, A.S., Mullikin, J.C., Gray, M.D., Stamatatos, L., Burton, D.R., Koff, W.C., Cohen, M.S., Haynes, B.F., Casazza, J.P., Connors, M., Corti, D., Lanzavecchia, A., Sattentau, Q.J., Weiss, R.A., West, A.P., Bjorkman, P.J., Scheid, J.F., Nussenzweig, M.C., Shapiro, L., Mascola, J.R., Kwong, P.D.

(2015) Cell 161: 1280-1292

  • DOI: https://doi.org/10.1016/j.cell.2015.05.007
  • Primary Citation of Related Structures:  
    4RWY, 4RX4, 4YDI, 4YDJ, 4YDK, 4YDL, 4YE4, 4YFL

  • PubMed Abstract: 

    The site on the HIV-1 gp120 glycoprotein that binds the CD4 receptor is recognized by broadly reactive antibodies, several of which neutralize over 90% of HIV-1 strains. To understand how antibodies achieve such neutralization, we isolated CD4-binding-site (CD4bs) antibodies and analyzed 16 co-crystal structures -8 determined here- of CD4bs antibodies from 14 donors. The 16 antibodies segregated by recognition mode and developmental ontogeny into two types: CDR H3-dominated and VH-gene-restricted. Both could achieve greater than 80% neutralization breadth, and both could develop in the same donor. Although paratope chemistries differed, all 16 gp120-CD4bs antibody complexes showed geometric similarity, with antibody-neutralization breadth correlating with antibody-angle of approach relative to the most effective antibody of each type. The repertoire for effective recognition of the CD4 supersite thus comprises antibodies with distinct paratopes arrayed about two optimal geometric orientations, one achieved by CDR H3 ontogenies and the other achieved by VH-gene-restricted ontogenies.

    • Organizational Affiliation: 

    Vaccine Research Center, National Institute of Allergy and Infectious Diseases and National Institutes of Health, Bethesda, MD 20892, USA.


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
HIV-1 Clade A Q842.d12 gp120A [auth G],
D [auth E]		354Human immunodeficiency virus 1Mutation(s): 0 
Gene Names: gp120
UniProt
Find proteins for Q8JDI3 (Human immunodeficiency virus 1)
Explore Q8JDI3 
Go to UniProtKB:  Q8JDI3
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ8JDI3
Sequence Annotations
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  • Reference Sequence
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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
8ANC134 Heavy chainB [auth H],
E [auth A]		229Homo sapiensMutation(s): 0 
Gene Names: 8ANC134 heavy chain
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  • Reference Sequence
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Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
8ANC134 Light ChainC [auth L],
F [auth D]		213Homo sapiensMutation(s): 0 
Gene Names: 8ANC134 light chain
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
NAG
Query on NAG
Download Ideal Coordinates CCD File 
AA [auth E]
G
H [auth G]
I [auth G]
J [auth G]
AA [auth E],
G,
H [auth G],
I [auth G],
J [auth G],
K [auth G],
L [auth G],
W [auth E],
X [auth E],
Y [auth E],
Z [auth E]
2-acetamido-2-deoxy-beta-D-glucopyranose
C8 H15 N O6
OVRNDRQMDRJTHS-FMDGEEDCSA-N
SO4
Query on SO4
Download Ideal Coordinates CCD File 
BA [auth E]
DA [auth A]
EA [auth D]
FA [auth D]
GA [auth D]
BA [auth E],
DA [auth A],
EA [auth D],
FA [auth D],
GA [auth D],
HA [auth D],
M [auth G],
Q [auth G],
R [auth G],
T [auth L],
U [auth L],
V [auth L]
SULFATE ION
O4 S
QAOWNCQODCNURD-UHFFFAOYSA-L
EDO
Query on EDO
Download Ideal Coordinates CCD File 
CA [auth E],
N [auth G],
O [auth G],
P [auth G],
S [auth G]		1,2-ETHANEDIOL
C2 H6 O2
LYCAIKOWRPUZTN-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.45 Å
  • R-Value Free: 0.253 
  • R-Value Work: 0.208 
  • R-Value Observed: 0.210 
  • Space Group: H 3
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 220.353α = 90
b = 220.353β = 90
c = 118.493γ = 120
Software Package:
Software NamePurpose
HKL-2000data collection
PHASERphasing
PHENIXrefinement
HKL-2000data reduction
HKL-2000data scaling

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2015-07-01
    Type: Initial release
  • Version 1.1: 2015-07-08
    Changes: Derived calculations
  • Version 1.2: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Data collection, Derived calculations, Structure summary
  • Version 1.3: 2021-06-02
    Changes: Source and taxonomy, Structure summary