IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v7y2016i1d10.1038_ncomms11813.html
   My bibliography  Save this article

Crystal structure of NOD2 and its implications in human disease

Author

Listed:
  • Sakiko Maekawa

    (Graduate School of Pharmaceutical Sciences, The University of Tokyo)

  • Umeharu Ohto

    (Graduate School of Pharmaceutical Sciences, The University of Tokyo)

  • Takuma Shibata

    (The Institute of Medical Science, The University of Tokyo)

  • Kensuke Miyake

    (The Institute of Medical Science, The University of Tokyo)

  • Toshiyuki Shimizu

    (Graduate School of Pharmaceutical Sciences, The University of Tokyo)

Abstract

Nucleotide-binding oligomerization domain-containing protein 2 (NOD2), a member of the NOD-like receptors family, are crucial for innate immune responses. Mutations of NOD2 have been associated with chronic inflammatory disorders such as Crohn’s disease (CD), Blau syndrome (BS) and early-onset sarcoidosis (EOS), but little is known about its signalling mechanism and the role it plays in these diseases. Here, we report the crystal structure of rabbit NOD2 in an ADP-bound state. The structure reveals an inactive closed conformation in which the subdomains in the NOD domain are closely packed by ADP-mediated and inter-domain interactions. Mapping of the BS- or EOS-associated gain-of-function mutations reveals that most of these mutations are located in the NOD subdomain interfaces, and are likely to disrupt the inner domain interactions, facilitating a conformational change to the active form. Conversely, mutations associated with CD are distributed throughout the protein, some of which may affect oligomer formation and ligand binding.

Suggested Citation

  • Sakiko Maekawa & Umeharu Ohto & Takuma Shibata & Kensuke Miyake & Toshiyuki Shimizu, 2016. "Crystal structure of NOD2 and its implications in human disease," Nature Communications, Nature, vol. 7(1), pages 1-11, September.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms11813
    DOI: 10.1038/ncomms11813
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms11813
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms11813?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:7:y:2016:i:1:d:10.1038_ncomms11813. 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.