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

  1. Jonathan M Wagner
  2. Marcin D Roganowicz
  3. Katarzyna Skorupka
  4. Steven L Alam
  5. Devin E Christensen
  6. Ginna L Doss
  7. Yueping Wan
  8. Gabriel A Frank
  9. Barbie K Ganser-Pornillos
  10. Wesley I Sundquist
  11. Owen Pornillos  Is a corresponding author
  1. University of Virginia, United States
  2. University of Utah, United States
  3. Ben-Gurion University, Israel
https://doi.org/10.7554/eLife.16309
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  1. Jonathan M Wagner
  2. Marcin D Roganowicz
  3. Katarzyna Skorupka
  4. Steven L Alam
  5. Devin E Christensen
  6. Ginna L Doss
  7. Yueping Wan
  8. Gabriel A Frank
  9. Barbie K Ganser-Pornillos
  10. Wesley I Sundquist
  11. Owen Pornillos
(2016)
Mechanism of B-box 2 domain-mediated higher-order assembly of the retroviral restriction factor TRIM5α
eLife 5:e16309.
https://doi.org/10.7554/eLife.16309
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Abstract

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.

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
    No competing interests declared.

  2. Marcin D Roganowicz

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

  3. Katarzyna Skorupka

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

  4. Steven L Alam

    Department of Biochemistry, University of Utah, Salt Lake City, 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. Ginna L Doss

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

  7. Yueping Wan

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

  8. Gabriel A Frank

    Department of Life Sciences and National Institute for Biotechnology in the Negev, Ben-Gurion University, Beer-Sheeva, Israel
    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. Wesley I Sundquist

    Department of Biochemistry, University of Utah, Salt Lake City, United States
    Competing interests
    Wesley I Sundquist, Reviewing editor, eLife.

  11. Owen Pornillos

    Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, United States
    For correspondence
    owp3a@eservices.virginia.edu
    Competing interests
    No competing interests declared.

Reviewing Editor

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

Version history

  1. Received: March 23, 2016
  2. Accepted: May 20, 2016
  3. Accepted Manuscript published: June 2, 2016 (version 1)
  4. Version of Record published: July 7, 2016 (version 2)

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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  1. Jonathan M Wagner
  2. Marcin D Roganowicz
  3. Katarzyna Skorupka
  4. Steven L Alam
  5. Devin E Christensen
  6. Ginna L Doss
  7. Yueping Wan
  8. Gabriel A Frank
  9. Barbie K Ganser-Pornillos
  10. Wesley I Sundquist
  11. Owen Pornillos
(2016)
Mechanism of B-box 2 domain-mediated higher-order assembly of the retroviral restriction factor TRIM5α
eLife 5:e16309.
https://doi.org/10.7554/eLife.16309

Share this article

https://doi.org/10.7554/eLife.16309

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