1. Structural Biology and Molecular Biophysics
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Nuclear export receptor CRM1 recognizes diverse conformations in nuclear export signals

  1. Ho Yee Joyce Fung
  2. Szu-chin Fu
  3. Yuh Min Chook  Is a corresponding author
  1. University of Texas Southwestern Medical Center, United States
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  • Views 2,125
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Cite this article as: eLife 2017;6:e23961 doi: 10.7554/eLife.23961

Abstract

Nuclear export receptor CRM1 binds highly variable nuclear export signals (NESs) in hundreds of different cargoes. Previously we have shown that CRM1 binds NESs in both polypeptide orientations (Fung et al., 2015). Here, we show crystal structures of CRM1 bound to eight additional NESs which reveal diverse conformations that range from loop-like to all-helix, which occupy different extents of the invariant NES-binding groove. Analysis of all NES structures show 5-6 distinct backbone conformations where the only conserved secondary structural element is one turn of helix that binds the central portion of the CRM1 groove. All NESs also participate in main chain hydrogen bonding with human CRM1 Lys568 side chain, which acts as a specificity filter that prevents binding of non-NES peptides. The large conformational range of NES backbones explains the lack of a fixed pattern for its 3-5 hydrophobic anchor residues, which in turn explains the large array of peptide sequences that can function as NESs.

Article and author information

Author details

  1. Ho Yee Joyce Fung

    Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0502-1957
  2. Szu-chin Fu

    Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Yuh Min Chook

    Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, United States
    For correspondence
    yuhmin.chook@utsouthwestern.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4974-0726

Funding

Howard Hughes Medical Institute (International Student Research fellow)

  • Ho Yee Joyce Fung

Croucher Foundation (Graduate Student Scholarship)

  • Ho Yee Joyce Fung

Cancer Prevention and Research Institute of Texas (RP120352)

  • Yuh Min Chook

Cancer Prevention and Research Institute of Texas (RP150053)

  • Yuh Min Chook

National Institutes of Health (R01 GM069909)

  • Yuh Min Chook

Welch Foundation (I-1532)

  • Yuh Min Chook

Leukemia and Lymphoma Society (Scholar Award)

  • Yuh Min Chook

University of Texas Southwestern Medical Center (Endowed Scholars Program)

  • Yuh Min Chook

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Mingjie Zhang, The Hong Kong University of Science and Technology, China

Publication history

  1. Received: December 6, 2016
  2. Accepted: March 9, 2017
  3. Accepted Manuscript published: March 10, 2017 (version 1)
  4. Version of Record published: March 20, 2017 (version 2)

Copyright

© 2017, Fung 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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