1. Immunology and Inflammation
  2. Microbiology and Infectious Disease
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Primate TRIM5 proteins form hexagonal nets 1 on HIV-1 capsids

  1. Yen-Li Li
  2. Viswanathan Chandrasekaran
  3. Stephen D Carter
  4. Cora L Woodward
  5. Devin E Christensen
  6. Kelly A Dryden
  7. Owen Pornillos
  8. Mark Yeager
  9. Barbie K Ganser-Pornillos
  10. Grant J Jensen
  11. Wesley I Sundquist  Is a corresponding author
  1. University of Utah, United States
  2. California Institute of Technology, United States
  3. University of Virginia, United States
Research Article
  • Cited 55
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Cite this article as: eLife 2016;5:e16269 doi: 10.7554/eLife.16269

Abstract

TRIM5 proteins are restriction factors that block retroviral infections by binding viral capsids and preventing reverse transcription. Capsid recognition is mediated by C-terminal domains on TRIM5α (SPRY) or TRIMCyp (cyclophilin A), which interact weakly with capsids. Efficient capsid recognition also requires the conserved N-terminal tripartite motifs (TRIM), which mediate oligomerization and create avidity effects. To characterize how TRIM5 proteins recognize viral capsids, we developed methods for isolating native recombinant TRIM5 proteins and purifying stable HIV-1 capsids. Biochemical and EM analyses revealed that TRIM5 proteins assembled into hexagonal nets, both alone and on capsid surfaces. These nets comprised open hexameric rings, with the SPRY domains centered on the edges and the B-box and RING domains at the vertices. Thus, the principles of hexagonal TRIM5 assembly and capsid pattern recognition are conserved across primates, allowing TRIM5 assemblies to maintain the conformational plasticity necessary to recognize divergent and pleomorphic retroviral capsids.

Article and author information

Author details

  1. Yen-Li Li

    Department of Biochemistry, University of Utah, Salt Lake City, United States
    Competing interests
    No competing interests declared.
  2. Viswanathan Chandrasekaran

    Department of Biochemistry, University of Utah, Salt Lake City, United States
    Competing interests
    No competing interests declared.
  3. Stephen D Carter

    Division of Biology, California Institute of Technology, Pasadena, United States
    Competing interests
    No competing interests declared.
  4. Cora L Woodward

    Division of Biology, California Institute of Technology, Pasadena, United States
    Competing interests
    No competing interests declared.
  5. Devin E Christensen

    Department of Biochemistry, University of Utah, Salt Lake City, United States
    Competing interests
    No competing interests declared.
  6. Kelly A Dryden

    Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, United States
    Competing interests
    No competing interests declared.
  7. Owen Pornillos

    Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, United States
    Competing interests
    No competing interests declared.
  8. Mark Yeager

    Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, United States
    Competing interests
    No competing interests declared.
  9. Barbie K Ganser-Pornillos

    Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, United States
    Competing interests
    No competing interests declared.
  10. Grant J Jensen

    Division of Biology, California Institute of Technology, Pasadena, United States
    Competing interests
    No competing interests declared.
  11. Wesley I Sundquist

    Department of Biochemistry, University of Utah, Salt Lake City, United States
    For correspondence
    wes@biochem.utah.edu
    Competing interests
    Wesley I Sundquist, Reviewing editor, eLife.

Reviewing Editor

  1. Stephen P Goff, Howard Hughes Medical Institute, Columbia University, United States

Publication history

  1. Received: March 22, 2016
  2. Accepted: May 19, 2016
  3. Accepted Manuscript published: June 2, 2016 (version 1)
  4. Accepted Manuscript updated: June 3, 2016 (version 2)
  5. Version of Record published: July 7, 2016 (version 3)

Copyright

© 2016, Li 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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