1. Biochemistry and Chemical Biology
  2. Microbiology and Infectious Disease

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
https://doi.org/10.7554/eLife.04120
Share this article
Cite this article
  1. Bhargavi Jayaraman
  2. David C Crosby
  3. Christina Homer
  4. Isabel Ribeiro
  5. David Mavor
  6. Alan D Frankel
(2014)
RNA-directed remodeling of the HIV-1 Rev protein orchestrates assembly of the Rev-Rev response element complex
eLife 3:e04120.
https://doi.org/10.7554/eLife.04120
  2. Download BibTeX
  3. Download .RIS

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

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, 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.

Metrics

  • 45,966
    Page views
  • 458
    Downloads
  • 54
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, Scopus, 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. Bhargavi Jayaraman
  2. David C Crosby
  3. Christina Homer
  4. Isabel Ribeiro
  5. David Mavor
  6. Alan D Frankel
(2014)
RNA-directed remodeling of the HIV-1 Rev protein orchestrates assembly of the Rev-Rev response element complex
eLife 3:e04120.
https://doi.org/10.7554/eLife.04120

Share this article

https://doi.org/10.7554/eLife.04120

Categories and tags

Research organism

Further reading

    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

    David S Booth, Yifan Cheng, Alan D Frankel
    Research Article Updated

    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.

    1. Microbiology and Infectious Disease

    Rev Protein: Really exasperating viral protein from HIV

    James R Williamson
    Insight

    Two new structures shed additional light on the nuclear transport of viral transcripts.

    1. Biochemistry and Chemical Biology
    2. Plant Biology

    Guanidine production by plant homoarginine-6-hydroxylases

    Dietmar Funck, Malte Sinn ... Jörg S Hartig
    Research Article

    Metabolism and biological functions of the nitrogen-rich compound guanidine have long been neglected. The discovery of four classes of guanidine-sensing riboswitches and two pathways for guanidine degradation in bacteria hint at widespread sources of unconjugated guanidine in nature. So far, only three enzymes from a narrow range of bacteria and fungi have been shown to produce guanidine, with the ethylene-forming enzyme (EFE) as the most prominent example. Here, we show that a related class of Fe2+- and 2-oxoglutarate-dependent dioxygenases (2-ODD-C23) highly conserved among plants and algae catalyze the hydroxylation of homoarginine at the C6-position. Spontaneous decay of 6-hydroxyhomoarginine yields guanidine and 2-aminoadipate-6-semialdehyde. The latter can be reduced to pipecolate by pyrroline-5-carboxylate reductase but more likely is oxidized to aminoadipate by aldehyde dehydrogenase ALDH7B in vivo. Arabidopsis has three 2-ODD-C23 isoforms, among which Din11 is unusual because it also accepted arginine as substrate, which was not the case for the other 2-ODD-C23 isoforms from Arabidopsis or other plants. In contrast to EFE, none of the three Arabidopsis enzymes produced ethylene. Guanidine contents were typically between 10 and 20 nmol*(g fresh weight)-1 in Arabidopsis but increased to 100 or 300 nmol*(g fresh weight)-1 after homoarginine feeding or treatment with Din11-inducing methyljasmonate, respectively. In 2-ODD-C23 triple mutants, the guanidine content was strongly reduced, whereas it increased in overexpression plants. We discuss the implications of the finding of widespread guanidine-producing enzymes in photosynthetic eukaryotes as a so far underestimated branch of the bio-geochemical nitrogen cycle and propose possible functions of natural guanidine production.