1. Biochemistry and Chemical Biology
  2. Structural Biology and Molecular Biophysics
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Crystal structure of an HIV assembly and maturation switch

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Cite this article as: eLife 2016;5:e17063 doi: 10.7554/eLife.17063

Abstract

Virus assembly and maturation proceeds through the programmed operation of molecular switches, which trigger both local and global structural rearrangements to produce infectious particles. HIV-1 contains an assembly and maturation switch that spans the C-terminal domain (CTD) of the capsid (CA) region and the first spacer peptide (SP1) of the precursor structural protein, Gag. The crystal structure of the CTD-SP1 Gag fragment is a goblet-shaped hexamer in which the cup comprises the CTD and an ensuing type II β-turn, and the stem comprises a 6-helix bundle. The β-turn is critical for immature virus assembly and the 6-helix bundle regulates proteolysis during maturation. This bipartite character explains why the SP1 spacer is a critical element of HIV-1 Gag but is not a universal property of retroviruses. Our results also indicate that HIV-1 maturation inhibitors prevent unfolding of the CA-SP1 junction and thereby deny access of the viral protease to its substrate.

Article and author information

Author details

  1. Jonathan M Wagner

    Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Kaneil K Zadrozny

    Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Jakub Chrustowicz

    Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Michael D Purdy

    Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Mark Yeager

    Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, United States
    For correspondence
    my3r@virginia.edu
    Competing interests
    The authors declare that no competing interests exist.
  6. Barbie K Ganser-Pornillos

    Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, United States
    For correspondence
    bpornillos@virginia.edu
    Competing interests
    The authors declare that no competing interests exist.
  7. Owen Pornillos

    Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, United States
    For correspondence
    owp3a@eservices.virginia.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9056-5002

Reviewing Editor

  1. Volker Dötsch, Goethe University, Germany

Publication history

  1. Received: April 19, 2016
  2. Accepted: June 13, 2016
  3. Accepted Manuscript published: July 14, 2016 (version 1)
  4. Version of Record published: July 15, 2016 (version 2)
  5. Version of Record updated: July 22, 2016 (version 3)

Copyright

© 2016, Wagner et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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