IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v6y2015i1d10.1038_ncomms8968.html
   My bibliography  Save this article

Multiple cellular proteins interact with LEDGF/p75 through a conserved unstructured consensus motif

Author

Listed:
  • Petr Tesina

    (Institute of Organic Chemistry and Biochemistry of the ASCR
    Faculty of Science, Charles University in Prague
    Institute of Molecular Genetics of the ASCR)

  • Kateřina Čermáková

    (KU Leuven, Molecular Virology and Gene Therapy)

  • Magdalena Hořejší

    (Institute of Molecular Genetics of the ASCR)

  • Kateřina Procházková

    (Institute of Organic Chemistry and Biochemistry of the ASCR)

  • Milan Fábry

    (Institute of Molecular Genetics of the ASCR)

  • Subhalakshmi Sharma

    (KU Leuven, Molecular Virology and Gene Therapy)

  • Frauke Christ

    (KU Leuven, Molecular Virology and Gene Therapy)

  • Jonas Demeulemeester

    (KU Leuven, Molecular Virology and Gene Therapy)

  • Zeger Debyser

    (KU Leuven, Molecular Virology and Gene Therapy)

  • Jan De Rijck

    (KU Leuven, Molecular Virology and Gene Therapy)

  • Václav Veverka

    (Institute of Organic Chemistry and Biochemistry of the ASCR)

  • Pavlína Řezáčová

    (Institute of Organic Chemistry and Biochemistry of the ASCR
    Institute of Molecular Genetics of the ASCR)

Abstract

Lens epithelium-derived growth factor (LEDGF/p75) is an epigenetic reader and attractive therapeutic target involved in HIV integration and the development of mixed lineage leukaemia (MLL1) fusion-driven leukaemia. Besides HIV integrase and the MLL1-menin complex, LEDGF/p75 interacts with various cellular proteins via its integrase binding domain (IBD). Here we present structural characterization of IBD interactions with transcriptional repressor JPO2 and domesticated transposase PogZ, and show that the PogZ interaction is nearly identical to the interaction of LEDGF/p75 with MLL1. The interaction with the IBD is maintained by an intrinsically disordered IBD-binding motif (IBM) common to all known cellular partners of LEDGF/p75. In addition, based on IBM conservation, we identify and validate IWS1 as a novel LEDGF/p75 interaction partner. Our results also reveal how HIV integrase efficiently displaces cellular binding partners from LEDGF/p75. Finally, the similar binding modes of LEDGF/p75 interaction partners represent a new challenge for the development of selective interaction inhibitors.

Suggested Citation

  • Petr Tesina & Kateřina Čermáková & Magdalena Hořejší & Kateřina Procházková & Milan Fábry & Subhalakshmi Sharma & Frauke Christ & Jonas Demeulemeester & Zeger Debyser & Jan De Rijck & Václav Veverka &, 2015. "Multiple cellular proteins interact with LEDGF/p75 through a conserved unstructured consensus motif," Nature Communications, Nature, vol. 6(1), pages 1-14, November.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms8968
    DOI: 10.1038/ncomms8968
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms8968
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms8968?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
    ---><---

    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:natcom:v:6:y:2015:i:1:d:10.1038_ncomms8968. 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.