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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
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    References listed on IDEAS

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    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.
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