8c82
Cryo-EM structure of the yeast SPT-Orm1-Dimer complex
Structural highlights
FunctionLCB1_YEAST Component of serine palmitoyltransferase (SPT), which catalyzes the committed step in the synthesis of sphingolipids, the condensation of serine with palmitoyl CoA to form the long chain base 3-ketosphinganine.[1] [2] Publication Abstract from PubMedSphingolipids 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. Structure of the ceramide-bound SPOTS complex.,Schafer JH, Korner C, Esch BM, Limar S, Parey K, Walter S, Januliene D, Moeller A, Frohlich F Nat Commun. 2023 Oct 4;14(1):6196. doi: 10.1038/s41467-023-41747-z. PMID:37794019[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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