IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v6y2015i1d10.1038_ncomms7129.html
   My bibliography  Save this article

Structural mechanism of ergosterol regulation by fungal sterol transcription factor Upc2

Author

Listed:
  • Huiseon Yang

    (College of Pharmacy, Chonnam National University)

  • Junsen Tong

    (College of Pharmacy, Chonnam National University)

  • Chul Won Lee

    (Chonnam National University)

  • Subin Ha

    (College of Pharmacy, Chonnam National University)

  • Soo Hyun Eom

    (School of Life Science, Steitz Center for Structural Biology, Gwangju Institute of Science and Technology)

  • Young Jun Im

    (College of Pharmacy, Chonnam National University)

Abstract

Transcriptional regulation of ergosterol biosynthesis in fungi is crucial for sterol homeostasis and for resistance to azole drugs. In Saccharomyces cerevisiae, the Upc2 transcription factor activates the expression of related genes in response to sterol depletion by poorly understood mechanisms. We have determined the structure of the C-terminal domain (CTD) of Upc2, which displays a novel α-helical fold with a deep hydrophobic pocket. We discovered that the conserved CTD is a ligand-binding domain and senses the ergosterol level in the cell. Ergosterol binding represses its transcription activity, while dissociation of the ligand leads to relocalization of Upc2 from cytosol to nucleus for transcriptional activation. The C-terminal activation loop is essential for ligand binding and for transcriptional regulation. Our findings highlight that Upc2 represents a novel class of fungal zinc cluster transcription factors, which can serve as a target for the developments of antifungal therapeutics.

Suggested Citation

  • Huiseon Yang & Junsen Tong & Chul Won Lee & Subin Ha & Soo Hyun Eom & Young Jun Im, 2015. "Structural mechanism of ergosterol regulation by fungal sterol transcription factor Upc2," Nature Communications, Nature, vol. 6(1), pages 1-13, May.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms7129
    DOI: 10.1038/ncomms7129
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms7129
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms7129?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_ncomms7129. 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.