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

Version 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.

Metrics

  • 4,724
    Page views
  • 950
    Downloads
  • 77
    Citations

Article citation count generated by polling the highest count across the following sources: Scopus, Crossref, PubMed Central.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  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

Further reading

    1. Structural Biology and Molecular Biophysics
    2. Microbiology and Infectious Disease
    Jeremy Luban
    Insight

    Structural studies reveal how an antiviral factor forms a molecular net to restrict retroviruses including HIV-1.

    1. Genetics and Genomics
    2. Immunology and Inflammation
    Xinjian Ye, Yijing Bai ... Qianming Chen
    Research Article

    Periodontitis drives irreversible destruction of periodontal tissue and is prone to exacerbating inflammatory disorders. Systemic immunomodulatory management continues to be an attractive approach in periodontal care, particularly within the context of ‘predictive, preventive, and personalized’ periodontics. The present study incorporated genetic proxies identified through genome-wide association studies for circulating immune cells and periodontitis into a comprehensive Mendelian randomization (MR) framework. Univariable MR, multivariable MR, subgroup analysis, reverse MR, and Bayesian model averaging (MR-BMA) were utilized to investigate the causal relationships. Furthermore, transcriptome-wide association study and colocalization analysis were deployed to pinpoint the underlying genes. Consequently, the MR study indicated a causal association between circulating neutrophils, natural killer T cells, plasmacytoid dendritic cells, and an elevated risk of periodontitis. MR-BMA analysis revealed that neutrophils were the primary contributors to periodontitis. The high-confidence genes S100A9 and S100A12, located on 1q21.3, could potentially serve as immunomodulatory targets for neutrophil-mediated periodontitis. These findings hold promise for early diagnosis, risk assessment, targeted prevention, and personalized treatment of periodontitis. Considering the marginal association observed in our study, further research is required to comprehend the biological underpinnings and ascertain the clinical relevance thoroughly.