Structure of the ceramide-bound SPOTS complex.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
04 10 2023
04 10 2023
Historique:
received:
03
02
2023
accepted:
05
09
2023
medline:
1
11
2023
pubmed:
5
10
2023
entrez:
4
10
2023
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 37794019
doi: 10.1038/s41467-023-41747-z
pii: 10.1038/s41467-023-41747-z
pmc: PMC10550967
doi:
Substances chimiques
Ceramides
0
Sphingolipids
0
Proteins
0
Serine C-Palmitoyltransferase
EC 2.3.1.50
Orm1 protein, S cerevisiae
0
Saccharomyces cerevisiae Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
6196Informations de copyright
© 2023. Springer Nature Limited.
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