IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-41747-z.html
   My bibliography  Save this article

Structure of the ceramide-bound SPOTS complex

Author

Listed:
  • Jan-Hannes Schäfer

    (Osnabrück University Department of Biology/Chemistry Structural Biology section)

  • Carolin Körner

    (Osnabrück University Department of Biology/Chemistry Bioanalytical Chemistry section)

  • Bianca M. Esch

    (Osnabrück University Department of Biology/Chemistry Bioanalytical Chemistry section)

  • Sergej Limar

    (Osnabrück University Department of Biology/Chemistry Bioanalytical Chemistry section)

  • Kristian Parey

    (Osnabrück University Department of Biology/Chemistry Structural Biology section
    Osnabrück University Center of Cellular Nanoanalytic Osnabrück (CellNanOs))

  • Stefan Walter

    (Osnabrück University Center of Cellular Nanoanalytic Osnabrück (CellNanOs))

  • Dovile Januliene

    (Osnabrück University Department of Biology/Chemistry Structural Biology section
    Osnabrück University Center of Cellular Nanoanalytic Osnabrück (CellNanOs))

  • Arne Moeller

    (Osnabrück University Department of Biology/Chemistry Structural Biology section
    Osnabrück University Center of Cellular Nanoanalytic Osnabrück (CellNanOs))

  • Florian Fröhlich

    (Osnabrück University Department of Biology/Chemistry Bioanalytical Chemistry section
    Osnabrück University Center of Cellular Nanoanalytic Osnabrück (CellNanOs))

Abstract

Sphingolipids are structural membrane components that also function in cellular stress responses. The serine palmitoyltransferase (SPT) catalyzes the rate-limiting step in sphingolipid biogenesis. Its activity is tightly regulated through multiple binding partners, including Tsc3, Orm proteins, ceramides, and the phosphatidylinositol-4-phosphate (PI4P) phosphatase Sac1. The structural organization and regulatory mechanisms of this complex are not yet understood. Here, we report the high-resolution cryo-EM structures of the yeast SPT in complex with Tsc3 and Orm1 (SPOT) as dimers and monomers and a monomeric complex further carrying Sac1 (SPOTS). In all complexes, the tight interaction of the downstream metabolite ceramide and Orm1 reveals the ceramide-dependent inhibition. Additionally, observation of ceramide and ergosterol binding suggests a co-regulation of sphingolipid biogenesis and sterol metabolism within the SPOTS complex.

Suggested Citation

  • Jan-Hannes Schäfer & Carolin Körner & Bianca M. Esch & Sergej Limar & Kristian Parey & Stefan Walter & Dovile Januliene & Arne Moeller & Florian Fröhlich, 2023. "Structure of the ceramide-bound SPOTS complex," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-41747-z
    DOI: 10.1038/s41467-023-41747-z
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-41747-z
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-41747-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. David K. Breslow & Sean R. Collins & Bernd Bodenmiller & Ruedi Aebersold & Kai Simons & Andrej Shevchenko & Christer S. Ejsing & Jonathan S. Weissman, 2010. "Orm family proteins mediate sphingolipid homeostasis," Nature, Nature, vol. 463(7284), pages 1048-1053, February.
    2. Joachim Moser von Filseck & Stefano Vanni & Bruno Mesmin & Bruno Antonny & Guillaume Drin, 2015. "A phosphatidylinositol-4-phosphate powered exchange mechanism to create a lipid gradient between membranes," Nature Communications, Nature, vol. 6(1), pages 1-12, May.
    3. Tian Xie & Peng Liu & Xinyue Wu & Feitong Dong & Zike Zhang & Jian Yue & Usha Mahawar & Faheem Farooq & Hisham Vohra & Qi Fang & Wenchen Liu & Binks W. Wattenberg & Xin Gong, 2023. "Ceramide sensing by human SPT-ORMDL complex for establishing sphingolipid homeostasis," Nature Communications, Nature, vol. 14(1), pages 1-14, 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. Tian Xie & Peng Liu & Xinyue Wu & Feitong Dong & Zike Zhang & Jian Yue & Usha Mahawar & Faheem Farooq & Hisham Vohra & Qi Fang & Wenchen Liu & Binks W. Wattenberg & Xin Gong, 2023. "Ceramide sensing by human SPT-ORMDL complex for establishing sphingolipid homeostasis," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    2. Yunyun Wang & Zhenni Li & Xinyu Wang & Ziyuan Zhao & Li Jiao & Ruming Liu & Keying Wang & Rui Ma & Yang Yang & Guo Chen & Yong Wang & Xin Bian, 2023. "Insights into membrane association of the SMP domain of extended synaptotagmin," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    3. Darshini Jeyasimman & Bilge Ercan & Dennis Dharmawan & Tomoki Naito & Jingbo Sun & Yasunori Saheki, 2021. "PDZD-8 and TEX-2 regulate endosomal PI(4,5)P2 homeostasis via lipid transport to promote embryogenesis in C. elegans," Nature Communications, Nature, vol. 12(1), pages 1-21, 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_s41467-023-41747-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.