1. Immunology and Inflammation
  2. Microbiology and Infectious Disease

Primate TRIM5 proteins form hexagonal nets 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
https://doi.org/10.7554/eLife.16269
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  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
(2016)
Primate TRIM5 proteins form hexagonal nets on HIV-1 capsids
eLife 5:e16269.
https://doi.org/10.7554/eLife.16269
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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.

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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.

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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  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
(2016)
Primate TRIM5 proteins form hexagonal nets on HIV-1 capsids
eLife 5:e16269.
https://doi.org/10.7554/eLife.16269

Share this article

https://doi.org/10.7554/eLife.16269

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Further reading

    1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics

    Mechanism of B-box 2 domain-mediated higher-order assembly of the retroviral restriction factor TRIM5α

    Jonathan M Wagner, Marcin D Roganowicz ... Owen Pornillos
    Research Article Updated

    Restriction factors and pattern recognition receptors are important components of intrinsic cellular defenses against viral infection. Mammalian TRIM5α proteins are restriction factors and receptors that target the capsid cores of retroviruses and activate ubiquitin-dependent antiviral responses upon capsid recognition. Here, we report crystallographic and functional studies of the TRIM5α B-box 2 domain, which mediates higher-order assembly of TRIM5 proteins. The B-box can form both dimers and trimers, and the trimers can link multiple TRIM5α proteins into a hexagonal net that matches the lattice arrangement of capsid subunits and enables avid capsid binding. Two modes of conformational flexibility allow TRIM5α to accommodate the variable curvature of retroviral capsids. B-box mediated interactions also modulate TRIM5α’s E3 ubiquitin ligase activity, by stereochemically restricting how the N-terminal RING domain can dimerize. Overall, these studies define important molecular details of cellular recognition of retroviruses, and how recognition links to downstream processes to disable the virus.

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