IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-44096-z.html
   My bibliography  Save this article

Orphan quality control by an SCF ubiquitin ligase directed to pervasive C-degrons

Author

Listed:
  • Ka-Yiu Edwin Kong

    (Institute of Molecular Biology (IMB))

  • Susmitha Shankar

    (Institute of Molecular Biology (IMB))

  • Frank Rühle

    (Institute of Molecular Biology (IMB))

  • Anton Khmelinskii

    (Institute of Molecular Biology (IMB))

Abstract

Selective protein degradation typically involves substrate recognition via short linear motifs known as degrons. Various degrons can be found at protein termini from bacteria to mammals. While N-degrons have been extensively studied, our understanding of C-degrons is still limited. Towards a comprehensive understanding of eukaryotic C-degron pathways, here we perform an unbiased survey of C-degrons in budding yeast. We identify over 5000 potential C-degrons by stability profiling of random peptide libraries and of the yeast C‑terminome. Combining machine learning, high-throughput mutagenesis and genetic screens reveals that the SCF ubiquitin ligase targets ~40% of degrons using a single F-box substrate receptor Das1. Although sequence-specific, Das1 is highly promiscuous, recognizing a variety of C-degron motifs. By screening for full-length substrates, we implicate SCFDas1 in degradation of orphan protein complex subunits. Altogether, this work highlights the variety of C-degron pathways in eukaryotes and uncovers how an SCF/C-degron pathway of broad specificity contributes to proteostasis.

Suggested Citation

  • Ka-Yiu Edwin Kong & Susmitha Shankar & Frank Rühle & Anton Khmelinskii, 2023. "Orphan quality control by an SCF ubiquitin ligase directed to pervasive C-degrons," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-44096-z
    DOI: 10.1038/s41467-023-44096-z
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-44096-z
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-44096-z?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. Saki Ichikawa & Hope A. Flaxman & Wenqing Xu & Nandini Vallavoju & Hannah C. Lloyd & Binyou Wang & Dacheng Shen & Matthew R. Pratt & Christina M. Woo, 2022. "The E3 ligase adapter cereblon targets the C-terminal cyclic imide degron," Nature, Nature, vol. 610(7933), pages 775-782, October.
    2. Anton Khmelinskii & Ewa Blaszczak & Marina Pantazopoulou & Bernd Fischer & Deike J. Omnus & Gaëlle Le Dez & Audrey Brossard & Alexander Gunnarsson & Joseph D. Barry & Matthias Meurer & Daniel Kirrmaie, 2014. "Protein quality control at the inner nuclear membrane," Nature, Nature, vol. 516(7531), pages 410-413, December.
    3. Bayan Mashahreh & Shir Armony & Kristoffer Enøe Johansson & Alon Chappleboim & Nir Friedman & Richard G. Gardner & Rasmus Hartmann-Petersen & Kresten Lindorff-Larsen & Tommer Ravid, 2022. "Conserved degronome features governing quality control associated proteolysis," Nature Communications, Nature, vol. 13(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.
    1. Gang Xue & Jianing Xie & Matthias Hinterndorfer & Marko Cigler & Lara Dötsch & Hana Imrichova & Philipp Lampe & Xiufen Cheng & Soheila Rezaei Adariani & Georg E. Winter & Herbert Waldmann, 2023. "Discovery of a Drug-like, Natural Product-Inspired DCAF11 Ligand Chemotype," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    2. Lene Clausen & Vasileios Voutsinos & Matteo Cagiada & Kristoffer E. Johansson & Martin Grønbæk-Thygesen & Snehal Nariya & Rachel L. Powell & Magnus K. N. Have & Vibe H. Oestergaard & Amelie Stein & Do, 2024. "A mutational atlas for Parkin proteostasis," Nature Communications, Nature, vol. 15(1), pages 1-17, December.

    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_s41467-023-44096-z. 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.