4HQQ

Crystal structure of RV144-elicited antibody CH58

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.40 Å
  • R-Value Free: 0.225 
  • R-Value Work: 0.183 
  • R-Value Observed: 0.185 

wwPDB Validation   3D Report Full Report


This is version 1.1 of the entry. See complete history. 


Literature

Vaccine Induction of Antibodies against a Structurally Heterogeneous Site of Immune Pressure within HIV-1 Envelope Protein Variable Regions 1 and 2.

Liao, H.X., Bonsignori, M., Alam, S.M., McLellan, J.S., Tomaras, G.D., Moody, M.A., Kozink, D.M., Hwang, K.K., Chen, X., Tsao, C.Y., Liu, P., Lu, X., Parks, R.J., Montefiori, D.C., Ferrari, G., Pollara, J., Rao, M., Peachman, K.K., Santra, S., Letvin, N.L., Karasavvas, N., Yang, Z.Y., Dai, K., Pancera, M., Gorman, J., Wiehe, K., Nicely, N.I., Rerks-Ngarm, S., Nitayaphan, S., Kaewkungwal, J., Pitisuttithum, P., Tartaglia, J., Sinangil, F., Kim, J.H., Michael, N.L., Kepler, T.B., Kwong, P.D., Mascola, J.R., Nabel, G.J., Pinter, A., Zolla-Pazner, S., Haynes, B.F.

(2013) Immunity 38: 176-186

  • DOI: https://doi.org/10.1016/j.immuni.2012.11.011
  • Primary Citation of Related Structures:  
    4HPO, 4HPY, 4HQQ

  • PubMed Abstract: 

    The RV144 HIV-1 trial of the canary pox vector (ALVAC-HIV) plus the gp120 AIDSVAX B/E vaccine demonstrated an estimated efficacy of 31%, which correlated directly with antibodies to HIV-1 envelope variable regions 1 and 2 (V1-V2). Genetic analysis of trial viruses revealed increased vaccine efficacy against viruses matching the vaccine strain at V2 residue 169. Here, we isolated four V2 monoclonal antibodies from RV144 vaccinees that recognize residue 169, neutralize laboratory-adapted HIV-1, and mediate killing of field-isolate HIV-1-infected CD4(+) T cells. Crystal structures of two of the V2 antibodies demonstrated that residue 169 can exist within divergent helical and loop conformations, which contrasted dramatically with the β strand conformation previously observed with a broadly neutralizing antibody PG9. Thus, RV144 vaccine-induced immune pressure appears to target a region that may be both sequence variable and structurally polymorphic. Variation may signal sites of HIV-1 envelope vulnerability, providing vaccine designers with new options.

    • Organizational Affiliation: 

    Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710, USA. hliao@duke.edu


Macromolecules
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(by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
CH58 Fab heavy chainA [auth H]231Homo sapiensMutation(s): 0 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
Sequence Annotations
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  • Reference Sequence
Find similar proteins by: 
(by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
CH58 Fab light chainB [auth L]216Homo sapiensMutation(s): 0 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
Sequence Annotations
Expand
  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.40 Å
  • R-Value Free: 0.225 
  • R-Value Work: 0.183 
  • R-Value Observed: 0.185 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 62.949α = 90
b = 70.44β = 90
c = 135.825γ = 90
Software Package:
Software NamePurpose
SERGUIdata 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: 2013-02-06
    Type: Initial release
  • Version 1.1: 2023-09-20
    Changes: Data collection, Database references, Refinement description