| Structural highlights
Function
LCB1_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 PubMed
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.
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
- ↑ Gable K, Han G, Monaghan E, Bacikova D, Natarajan M, Williams R, Dunn TM. Mutations in the yeast LCB1 and LCB2 genes, including those corresponding to the hereditary sensory neuropathy type I mutations, dominantly inactivate serine palmitoyltransferase. J Biol Chem. 2002 Mar 22;277(12):10194-200. PMID:11781309 doi:10.1074/jbc.M107873200
- ↑ Nagiec MM, Baltisberger JA, Wells GB, Lester RL, Dickson RC. The LCB2 gene of Saccharomyces and the related LCB1 gene encode subunits of serine palmitoyltransferase, the initial enzyme in sphingolipid synthesis. Proc Natl Acad Sci U S A. 1994 Aug 16;91(17):7899-902. PMID:8058731 doi:10.1073/pnas.91.17.7899
- ↑ Schäfer JH, Körner C, Esch BM, Limar S, Parey K, Walter S, Januliene D, Moeller A, Fröhlich F. Structure of the ceramide-bound SPOTS complex. Nat Commun. 2023 Oct 4;14(1):6196. PMID:37794019 doi:10.1038/s41467-023-41747-z
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