IDEAS home Printed from https://ideas.repec.org/a/nat/nature/v458y2009i7242d10.1038_nature07975.html
   My bibliography  Save this article

Structural basis for leucine-rich nuclear export signal recognition by CRM1

Author

Listed:
  • Xiuhua Dong

    (University of Texas Southwestern Medical Center at Dallas, 6001 Forest Park, Dallas, Texas 75390-9041, USA)

  • Anindita Biswas

    (University of Texas Southwestern Medical Center at Dallas, 6001 Forest Park, Dallas, Texas 75390-9041, USA)

  • Katherine E. Süel

    (University of Texas Southwestern Medical Center at Dallas, 6001 Forest Park, Dallas, Texas 75390-9041, USA)

  • Laurie K. Jackson

    (University of Texas Southwestern Medical Center at Dallas, 6001 Forest Park, Dallas, Texas 75390-9041, USA)

  • Rita Martinez

    (University of Texas Southwestern Medical Center at Dallas, 6001 Forest Park, Dallas, Texas 75390-9041, USA)

  • Hongmei Gu

    (University of Texas Southwestern Medical Center at Dallas, 6001 Forest Park, Dallas, Texas 75390-9041, USA)

  • Yuh Min Chook

    (University of Texas Southwestern Medical Center at Dallas, 6001 Forest Park, Dallas, Texas 75390-9041, USA)

Abstract

CRM1 (also known as XPO1 and exportin 1) mediates nuclear export of hundreds of proteins through the recognition of the leucine-rich nuclear export signal (LR-NES). Here we present the 2.9 Å structure of CRM1 bound to snurportin 1 (SNUPN). Snurportin 1 binds CRM1 in a bipartite manner by means of an amino-terminal LR-NES and its nucleotide-binding domain. The LR-NES is a combined α-helical-extended structure that occupies a hydrophobic groove between two CRM1 outer helices. The LR-NES interface explains the consensus hydrophobic pattern, preference for intervening electronegative residues and inhibition by leptomycin B. The second nuclear export signal epitope is a basic surface on the snurportin 1 nucleotide-binding domain, which binds an acidic patch on CRM1 adjacent to the LR-NES site. Multipartite recognition of individually weak nuclear export signal epitopes may be common to CRM1 substrates, enhancing CRM1 binding beyond the generally low affinity LR-NES. Similar energetic construction is also used in multipartite nuclear localization signals to provide broad substrate specificity and rapid evolution in nuclear transport.

Suggested Citation

  • Xiuhua Dong & Anindita Biswas & Katherine E. Süel & Laurie K. Jackson & Rita Martinez & Hongmei Gu & Yuh Min Chook, 2009. "Structural basis for leucine-rich nuclear export signal recognition by CRM1," Nature, Nature, vol. 458(7242), pages 1136-1141, April.
    • Handle: RePEc:nat:nature:v:458:y:2009:i:7242:d:10.1038_nature07975
    DOI: 10.1038/nature07975
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/nature07975
    File Function: Abstract
    Download Restriction: Access to the full text of the articles in this series is restricted.
    File URL: https://libkey.io/10.1038/nature07975?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    As the access to this document is restricted, you may want to search for a different version of it.

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Shunichi Kosugi & Hiroshi Yanagawa & Ryohei Terauchi & Satoshi Tabata, 2014. "NESmapper: Accurate Prediction of Leucine-Rich Nuclear Export Signals Using Activity-Based Profiles," PLOS Computational Biology, Public Library of Science, vol. 10(9), pages 1-11, September.
    2. Qi Ye & Jian Ma & Zixi Wang & Lei Li & Tianjie Liu & Bin Wang & Lizhe Zhu & Yuzeshi Lei & Shan Xu & Ke Wang & Yanlin Jian & Bohan Ma & Yizeng Fan & Jing Liu & Yang Gao & Haojie Huang & Lei Li, 2024. "DTX3L-mediated TIRR nuclear export and degradation regulates DNA repair pathway choice and PARP inhibitor sensitivity," Nature Communications, Nature, vol. 15(1), pages 1-15, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:nature:v:458:y:2009:i:7242:d:10.1038_nature07975. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.