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Crystal structure of a non-neutralizing antibody to the HIV-1 gp41 membrane-proximal external region

Nature Structural & Molecular Biology volume 17, pages 1492–1494 (2010)Cite this article

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Abstract

The monoclonal antibody 13H11 shares part of its epitope in the HIV-1 gp41 membrane-proximal external region (MPER) with the rare, broadly neutralizing human antibody 2F5. Although 13H11 partially cross-blocked 2F5 binding, 13H11 is non-neutralizing and does not block 2F5 neutralization. We show that unlike 2F5, 13H11 binds to a well-defined helical MPER structure that is consistent with the structure of gp41 in a post-fusion six-helix bundle conformation.

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Figure 1: Structure of 13H11 Fab.
Figure 2: Structure of 13H11 bound to MPER.
Figure 3: Relevance to the post-fusion six-helix bundle.

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Acknowledgements

This work was supported by a Collaboration for AIDS Vaccine Discovery grant to B.F.H. from the Bill and Melinda Gates Foundation. Crystallography was done in the Duke University X-ray Crystallography Shared Resource. Use of the Advanced Photon Source was supported by the US Department of Energy, Office of Science, Office of Basic Energy Sciences, under Contract No. W-31-109-Eng-38. Supporting institutions may be found at http://www.ser-cat.org/members.html. We thank B. Chen (Children's Hospital and Department of Pediatrics, Harvard Medical School) for the gp41-inter protein as well as T. Oas and B. Fronch for assistance with circular dichroism.

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Authors and Affiliations

  1. Duke Human Vaccine Institute, Duke University School of Medicine, Durham, North Carolina, USA

    Nathan I Nicely, S Moses Dennison, Richard M Scearce, Haiyan Chen, Hua-Xin Liao, S Munir Alam & Barton F Haynes

  2. Departments of Biochemistry and Radiology, Duke University, Durham, North Carolina, USA

    Leonard Spicer

  3. Department of Immunology, Duke University and Duke Human Vaccine Institute, Duke University School of Medicine, Durham, North Carolina, USA

    Garnett Kelsoe & Yoshihiro Ueda

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  1. Nathan I Nicely
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Contributions

N.I.N. purified proteins and carried out all crystallographic processes and analyses. H.C. and H.-X.L. designed the expression system and produced proteins. S.M.D. and S.M.A. did the binding kinetics measurements and analyses. L.S. assisted in review of the data. B.F.H. and R.M.S. made the mAb 13H11. Y.U. and G.K. sequenced mAb 13H11 VH and VL genes. B.F.H. was responsible for project design and leadership. N.I.N., S.M.A. and B.F.H. wrote the manuscript. N.I.N., S.M.D. and S.M.A. generated the figures.

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Correspondence to Nathan I Nicely or Barton F Haynes.

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The authors declare no competing financial interests.

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Supplementary Text and Figures

Supplementary Figures 1–4, Supplementary Tables 1–3, Supplementary Results and Supplementary Methods (PDF 826 kb)

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Nicely, N., Dennison, S., Spicer, L. et al. Crystal structure of a non-neutralizing antibody to the HIV-1 gp41 membrane-proximal external region. Nat Struct Mol Biol 17, 1492–1494 (2010). https://doi.org/10.1038/nsmb.1944

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