IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-42823-0.html
   My bibliography  Save this article

Structures of the DarR transcription regulator reveal unique modes of second messenger and DNA binding

Author

Listed:
  • Maria A. Schumacher

    (Duke University School of Medicine)

  • Nicholas Lent

    (Duke University School of Medicine)

  • Vincent B. Chen

    (Duke University School of Medicine)

  • Raul Salinas

    (Duke University School of Medicine)

Abstract

The mycobacterial repressor, DarR, a TetR family regulator (TFR), was the first transcription regulator shown to bind c-di-AMP. However, the molecular basis for this interaction and the mechanism involved in DNA binding by DarR remain unknown. Here we describe DarR-c-di-AMP and DarR-DNA structures and complementary biochemical assays. The DarR-c-di-AMP structure reveals a unique effector binding site for a TFR, located between DarR dimer subunits. Strikingly, we show this motif also binds cAMP. The location of the adenine nucleotide binding site between subunits suggests this interaction may facilitate dimerization and hence DNA binding. Indeed, biochemical assays show cAMP enhances DarR DNA binding. Finally, DarR-DNA structures reveal a distinct TFR DNA-binding mechanism involving two interacting dimers on the DNA. Thus, the combined data unveil a newly described second messenger binding motif and DNA binding mode for this important family of regulators.

Suggested Citation

  • Maria A. Schumacher & Nicholas Lent & Vincent B. Chen & Raul Salinas, 2023. "Structures of the DarR transcription regulator reveal unique modes of second messenger and DNA binding," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-42823-0
    DOI: 10.1038/s41467-023-42823-0
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-42823-0
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-42823-0?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
    ---><---

    References listed on IDEAS

    as
    1. Julia Lara & Lautaro Diacovich & Felipe Trajtenberg & Nicole Larrieux & Emilio L. Malchiodi & Marisa M. Fernández & Gabriela Gago & Hugo Gramajo & Alejandro Buschiazzo, 2020. "Mycobacterium tuberculosis FasR senses long fatty acyl-CoA through a tunnel and a hydrophobic transmission spine," Nature Communications, Nature, vol. 11(1), pages 1-13, December.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.

      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:14:y:2023:i:1:d:10.1038_s41467-023-42823-0. 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.

      If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with 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.