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Localization of VP4 neutralization sites in rotavirus by three-dimensional cryo-electron microscopy

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Abstract

THREE-DIMENSIONAL structures of several spherical viruses have been determined by electron microscopy1–6 and X-ray crystallography7,8. We report here the first three-dimensional structure of the complex between an intact virus and Fab fragments of a neutralizing monoclonal antibody. The antibody is against VP4, one of the two outer capsid proteins of rotaviruses. These large icosahedral viruses cause gastroenteritis in children and young animals and account for over a million human deaths annually9. VP4 in these viruses has been implicated in several important functions such as cell penetration, haemagglutination, neutralization and virulence10–12. Here we demonstrate that the surface spikes on rotavirus particles are made up of VP4. Antigenic sites are located near the distal ends of the spikes and two Fab fragments bind to each of the sixty spikes. The mass of the spike indicates that it is a dimer of VP4. The bilobed structure at the distal end of the spike may be involved in both the attachment to the cell and in viral penetration. A novel feature in the virus–Fab complex is the structural difference between the two chemically equivalent Fab fragments on each spike, which could be indicative of variations in the Fab elbow angles.

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Author notes

  1. J. W. Burns

    Present address: Department of Immunology, Scripps Clinic and Research Institute, La Jolla, California, 92037, USA

Authors and Affiliations

  1. Verna and Marrs McLean Department of Biochemistry, Baylor College of Medicine, Houston, Texas, 77030, USA

    B. V. Venkataram Prasad, E. Marietta & W. Chiu

  2. Division of Molecular Virology, Baylor College of Medicine, Houston, Texas, 77030, USA

    J. W. Burns, M. K. Estes & W. Chiu

Authors
  1. B. V. Venkataram Prasad
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  2. J. W. Burns
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  3. E. Marietta
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  4. M. K. Estes
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  5. W. Chiu
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Prasad, B., Burns, J., Marietta, E. et al. Localization of VP4 neutralization sites in rotavirus by three-dimensional cryo-electron microscopy. Nature 343, 476–479 (1990). https://doi.org/10.1038/343476a0

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