IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v8y2017i1d10.1038_ncomms14004.html
   My bibliography  Save this article

Structural basis for the recognition and degradation of host TRIM proteins by Salmonella effector SopA

Author

Listed:
  • Evgenij Fiskin

    (Institute of Biochemistry II, Goethe University School of Medicine)

  • Sagar Bhogaraju

    (Institute of Biochemistry II, Goethe University School of Medicine
    Buchmann Institute for Molecular Life Sciences, Goethe University)

  • Lina Herhaus

    (Institute of Biochemistry II, Goethe University School of Medicine)

  • Sissy Kalayil

    (Institute of Biochemistry II, Goethe University School of Medicine
    Buchmann Institute for Molecular Life Sciences, Goethe University)

  • Marcel Hahn

    (Institute of Biochemistry II, Goethe University School of Medicine)

  • Ivan Dikic

    (Institute of Biochemistry II, Goethe University School of Medicine
    Buchmann Institute for Molecular Life Sciences, Goethe University
    School of Medicine, University of Split)

Abstract

The hallmark of Salmonella Typhimurium infection is an acute intestinal inflammatory response, which is mediated through the action of secreted bacterial effector proteins. The pro-inflammatory Salmonella effector SopA is a HECT-like E3 ligase, which was previously proposed to activate host RING ligases TRIM56 and TRIM65. Here we elucidate an inhibitory mechanism of TRIM56 and TRIM65 targeting by SopA. We present the crystal structure of SopA in complex with the RING domain of human TRIM56, revealing the atomic details of their interaction and the basis for SopA selectivity towards TRIM56 and TRIM65. Structure-guided biochemical analysis shows that SopA inhibits TRIM56 E3 ligase activity by occluding the E2-interacting surface of TRIM56. We further demonstrate that SopA ubiquitinates TRIM56 and TRIM65, resulting in their proteasomal degradation during infection. Our results provide the basis for how a bacterial HECT ligase blocks host RING ligases and exemplifies the multivalent power of bacterial effectors during infection.

Suggested Citation

  • Evgenij Fiskin & Sagar Bhogaraju & Lina Herhaus & Sissy Kalayil & Marcel Hahn & Ivan Dikic, 2017. "Structural basis for the recognition and degradation of host TRIM proteins by Salmonella effector SopA," Nature Communications, Nature, vol. 8(1), pages 1-14, April.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms14004
    DOI: 10.1038/ncomms14004
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms14004
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms14004?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:8:y:2017:i:1:d:10.1038_ncomms14004. 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.