EMD-16469
Cryo-EM structure of the yeast SPT-Orm1-Dimer complex
EMD-16469
Single-particle3.4 Å
Deposition: 18/01/2023Map released: 11/10/2023
Last modified: 11/10/2023
Sample Organism:
Saccharomyces cerevisiae
Sample: Complex of Orm1 with Lcb1, Lcb2 and Tsc3
Fitted models: 8c82 (Avg. Q-score: 0.488)
Deposition Authors: Schaefer J, Koerner C, Parey K
,
Januliene D ,
Moeller A ,
Froehlich F
Sample: Complex of Orm1 with Lcb1, Lcb2 and Tsc3
Fitted models: 8c82 (Avg. Q-score: 0.488)
Deposition Authors: Schaefer J, Koerner C, Parey K
,
Januliene D ,
Moeller A ,
Froehlich F
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
(2023) Nat Commun , 14 , 6196 - 6196
,
Korner C,
Esch BM,
Limar S,
Parey K ,
Walter S ,
Januliene D ,
Moeller A ,
Frohlich F
(2023) Nat Commun , 14 , 6196 - 6196
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.
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.