1. Structural Biology and Molecular Biophysics
  2. Microbiology and Infectious Disease

The export receptor Crm1 forms a dimer to promote nuclear export of HIV RNA

  1. David S Booth
  2. Yifan Cheng
  3. Alan D Frankel  Is a corresponding author
  1. University of California, San Francisco, United States
https://doi.org/10.7554/eLife.04121
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  1. David S Booth
  2. Yifan Cheng
  3. Alan D Frankel
(2014)
The export receptor Crm1 forms a dimer to promote nuclear export of HIV RNA
eLife 3:e04121.
https://doi.org/10.7554/eLife.04121
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Abstract

The HIV Rev protein routes viral RNAs containing the Rev Response Element (RRE) through the Crm1 nuclear export pathway to the cytoplasm where viral proteins are expressed and genomic RNA is delivered to assembling virions. The RRE assembles a Rev oligomer that displays nuclear export sequences (NESs) for recognition by the Crm1-RanGTP nuclear receptor complex. Here we provide the first view of an assembled HIV-host nuclear export complex using single-particle electron microscopy. Unexpectedly, Crm1 forms a dimer with an extensive interface that enhances association with Rev-RRE and poises NES binding sites to interact with a Rev oligomer. The interface between Crm1 monomers explains differences between Crm1 orthologs that alter nuclear export and determine cellular tropism for viral replication. The arrangement of the export complex identifies a novel binding surface to possibly target an HIV inhibitor and may point to a broader role for Crm1 dimerization in regulating host gene expression.

Article and author information

Author details

  1. David S Booth

    Graduate Group in Biophysics, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.

  2. Yifan Cheng

    Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.

  3. Alan D Frankel

    Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, United States
    For correspondence
    frankel@cgl.ucsf.edu
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Wesley I Sundquist, University of Utah, United States

Version history

  1. Received: July 22, 2014
  2. Accepted: December 6, 2014
  3. Accepted Manuscript published: December 8, 2014 (version 1)
  4. Version of Record published: January 9, 2015 (version 2)

Copyright

© 2014, Booth 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. David S Booth
  2. Yifan Cheng
  3. Alan D Frankel
(2014)
The export receptor Crm1 forms a dimer to promote nuclear export of HIV RNA
eLife 3:e04121.
https://doi.org/10.7554/eLife.04121

Share this article

https://doi.org/10.7554/eLife.04121

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Further reading

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    RNA-directed remodeling of the HIV-1 protein Rev orchestrates assembly of the Rev–Rev response element complex

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