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Image reconstructions of helical assemblies of the HIV-1 CA protein

Nature volume 407, pages 409–413 (2000)Cite this article

Abstract

The type 1 human immunodeficiency virus (HIV-1) contains a conical capsid comprising ∼1,500 CA protein subunits, which organizes the viral RNA genome for uncoating and replication in a new host cell. In vitro, CA spontaneously assembles into helical tubes and cones that resemble authentic viral capsids1,2,3,4,5,6,7. Here we describe electron cryo-microscopy and image reconstructions of CA tubes from six different helical families. In spite of their polymorphism, all tubes are composed of hexameric rings of CA arranged with approximate local p6 lattice symmetry. Crystal structures of the two CA domains were ‘docked’ into the reconstructed density, which showed that the amino-terminal domains form the hexameric rings and the carboxy-terminal dimerization domains connect each ring to six neighbours. We propose a molecular model for the HIV-1 capsid that follows the principles of a fullerene cone6, in which the body of the cone is composed of curved hexagonal arrays of CA rings and the ends are closed by inclusion of 12 pentagonal ‘defects’.

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Figure 1: Electron cryo-micrographs and image reconstructions of HIV-1 CA assemblies.
Figure 2: Reconstructed density and molecular modelling of a CA tube.
Figure 3: CA helical family polymorphism and cone formation.

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Acknowledgements

We thank W. Clemons, B. Ganser, J. Smith, C. Villa and D. Worthylake for technical assistance; J. Berriman for help and advice with data collection; and M. Stowell and N. Unwin for guidance in the use of their image reconstruction software. We also thank N. Unwin and R. Henderson for critical reading of our manuscript; and H.-G. Kräusslich for communicating results before publication. This research was supported by the MRC (UK) and by the NIH (US).

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Authors and Affiliations

  1. Department of Biochemistry, University of Utah, Salt Lake City, 84132, Utah, USA

    Su Li, Christopher P. Hill & Wesley I. Sundquist

  2. Division of Structural Studies, MRC Laboratory of Molecular Biology, Hills Road, Cambridge, CB2 2QH, UK

    John T. Finch

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  1. Su Li
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  2. Christopher P. Hill
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Correspondence to Wesley I. Sundquist.

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Li, S., Hill, C., Sundquist, W. et al. Image reconstructions of helical assemblies of the HIV-1 CA protein. Nature 407, 409–413 (2000). https://doi.org/10.1038/35030177

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