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Structure of the Epstein-Barr virus major envelope glycoprotein

Nature Structural & Molecular Biology volume 13, pages 9961001 (2006) | Download Citation

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Abstract

Epstein-Barr virus (EBV) infection of B cells is associated with lymphoma and other human cancers. EBV infection is initiated by the binding of the viral envelope glycoprotein (gp350) to the cell surface receptor CR2. We determined the X-ray structure of the highly glycosylated gp350 and defined the CR2 binding site on gp350. Polyglycans shield all but one surface of the gp350 polypeptide, and we demonstrate that this glycan-free surface is the receptor-binding site. Deglycosylated gp350 bound CR2 similarly to the glycosylated form, suggesting that glycosylation is not important for receptor binding. Structure-guided mutagenesis of the glycan-free surface disrupted receptor binding as well as binding by a gp350 monoclonal antibody, a known inhibitor of virus-receptor interactions. These results provide structural information for developing drugs and vaccines to prevent infection by EBV and related viruses.

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Acknowledgements

The work was supported by US National Institutes of Health grants R01AI050096 to X.S.C. and R0-1 R01CA053615 to V.M.H. We thank staff scientists at the 19ID beamline at the Structural Biology Center in Argonne National Laboratory and at Advanced Light Source beamlines BL8.2.1 and BL 8.2.2 for assistance in data collection.

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Affiliations

  1. Department of Molecular and Computational Biology, University of Southern California, 1050 Childs Way, Los Angeles, California 90089, USA.

    • Gerda Szakonyi
    • , Michael G Klein
    •  & Xiaojiang S Chen
  2. University of Szeged, Institute of Pharmaceutical Analysis, Szeged, 6720, Hungary.

    • Gerda Szakonyi
  3. Department of Medicine and Immunology, University of Colorado Health Sciences Center, 4200 E 9th Ave., Denver, Colorado 80262, USA.

    • Jonathan P Hannan
    • , Kendra A Young
    • , Rengasamy Asokan
    •  & V Michael Holers
  4. Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.

    • Runlin Z Ma

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Contributions

G.S. purified the proteins, grew the crystals, collected data, solved the phases and built the initial model. M.G.K. improved the phases and refined the model. J.P.H. and K.A.Y. made the mutants and conducted the binding studies. R.Z.M. generated antibodies for cloning and expression of gp350. R.A. helped with the initial protein purification. V.M.H. participated in the experimental design and data analysis. X.S.C. supervised the entire project.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Xiaojiang S Chen.

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https://doi.org/10.1038/nsmb1161

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