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Conserved structural elements in the V3 crown of HIV-1 gp120

Nature Structural & Molecular Biology volume 17, pages 955961 (2010) | Download Citation

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Abstract

Binding of the third variable region (V3) of the HIV-1 envelope glycoprotein gp120 to the cell-surface coreceptors CCR5 or CXCR4 during viral entry suggests that there are conserved structural elements in this sequence-variable region. These conserved elements could serve as epitopes to be targeted by a vaccine against HIV-1. Here we perform a systematic structural analysis of representative human anti-V3 monoclonal antibodies in complex with V3 peptides, revealing that the crown of V3 has four conserved structural elements: an arch, a band, a hydrophobic core and the peptide backbone. These are either unaffected by or are subject to minimal sequence variation. As these regions are targeted by cross-clade neutralizing human antibodies, they provide a blueprint for the design of vaccine immunogens that could elicit broadly cross-reactive protective antibodies.

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Change history

  • 21 July 2010

    In the version of this article initially published online, 4 residues should have read 13. In addition in figure 1a, circulet should have read circlet. These errors have been corrected for the print, PDF and HTML versions of this article.

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Acknowledgements

We thank R. Allison, formerly Press Secretary to Queen Elizabeth II, for providing the definition of the regions of the crown, as exemplified by the St. Edward's crown worn by Edward the Confessor, J. Sampson for assisting with the structure refinement and figure preparation, T. O'Neal and X.-H. Wang for antibody production and sequence analysis, staff members at beamlines X4A, X4C and X6A at the National Synchrotron Light Source for X-ray diffraction data collections and C. Hioe and N. Cowan for critical comments on the work and manuscript. This study was supported in part by the Bill and Melinda Gates Foundation, US National Institutes of Health grants AI36085 and HL59725, the Immunology Core of the New York University Center for AIDS Research (US National Institutes of Health grant AI27742) and by research funds from the US Department of Veterans Affairs.

Author information

Author notes

    • Xunqing Jiang
    •  & Valicia Burke

    These authors contributed equally to this work.

Affiliations

  1. Department of Biochemistry, New York University School of Medicine, New York, New York, USA.

    • Xunqing Jiang
    • , Valicia Burke
    •  & Xiang-Peng Kong
  2. Molsoft LLC, La Jolla, California, USA.

    • Maxim Totrov
  3. Department of Pathology, New York University School of Medicine, New York, New York, USA.

    • Constance Williams
    • , Miroslaw K Gorny
    •  & Susan Zolla-Pazner
  4. Department of Pharmacology, New York University School of Medicine, New York, New York, USA.

    • Timothy Cardozo
  5. Veterans Affairs New York Harbor Healthcare System, New York, New York, USA.

    • Susan Zolla-Pazner

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Contributions

X.J. and V.B. crystallized the complexes and collected the X-ray data; M.T. designed the V3 mimotope; C.W. produced the mAbs; T.C., M.K.G., S.Z.-P. and X.-P.K. designed the experiments; S.Z.-P. and X.-P.K. wrote the manuscript; all authors discussed the results and commented on the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Xiang-Peng Kong.

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https://doi.org/10.1038/nsmb.1861

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