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-Structure paper
Title | Structure of the ceramide-bound SPOTS complex. |
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Journal, issue, pages | Nat Commun, Vol. 14, Issue 1, Page 6196, Year 2023 |
Publish date | Oct 4, 2023 |
Authors | Jan-Hannes Schäfer / Carolin Körner / Bianca M Esch / Sergej Limar / Kristian Parey / Stefan Walter / Dovile Januliene / Arne Moeller / Florian Fröhlich / |
PubMed 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. ...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. |
External links | Nat Commun / PubMed:37794019 / PubMed Central |
Methods | EM (single particle) |
Resolution | 3.0 - 3.4 Å |
Structure data | EMDB-16467, PDB-8c80: EMDB-16468, PDB-8c81: EMDB-16469, PDB-8c82: EMDB-16485: Cryo-EM structure of the yeast SPT-Orm1-Dimer complex, local refinement of a monomer |
Chemicals | ChemComp-ERG: ChemComp-Z8A: ChemComp-PLP: ChemComp-Q7G: |
Source |
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Keywords | TRANSFERASE / Serine-Palmitoyl-Transferase / SPT / Orm-Protein |