1. Biochemistry and Chemical Biology
  2. Microbiology and Infectious Disease
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RNA-directed remodeling of the HIV-1 Rev protein orchestrates assembly of the Rev-Rev response element complex

  1. Bhargavi Jayaraman
  2. David C Crosby
  3. Christina Homer
  4. Isabel Ribeiro
  5. David Mavor
  6. Alan D Frankel  Is a corresponding author
  1. University of California, San Francisco, United States
Research Article
  • Cited 33
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Cite this article as: eLife 2014;3:e04120 doi: 10.7554/eLife.04120

Abstract

The HIV-1 protein Rev controls a critical step in viral replication by mediating the nuclear export of unspliced and singly-spliced viral mRNAs. Multiple Rev subunits assemble on the Rev Response Element (RRE), a structured region present in these RNAs, and direct their export through the Crm1 pathway. Rev-RRE assembly occurs via several Rev oligomerization and RNA-binding steps, but how these steps are coordinated to form an export-competent complex is unclear. Here, we report the first crystal structure of a Rev dimer-RRE complex, revealing a dramatic rearrangement of the Rev-dimer upon RRE binding through re-packing of its hydrophobic protein-protein interface. Rev-RNA recognition relies on sequence-specific contacts at the well-characterized IIB site and local RNA architecture at the second site. The structure supports a model in which the RRE utilizes the inherent plasticity of Rev subunit interfaces to guide the formation of a functional complex.

Article and author information

Author details

  1. Bhargavi Jayaraman

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

    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. Christina Homer

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

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

    Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. 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

Publication 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, Jayaraman 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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