ArticleNature structural & molecular biology2021
Structural insights into the regulation of human serine palmitoyltransferase complexes.
Article in Nature structural & molecular biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed.
- Compound Z247611722 Exhibits Antifungal Activity by Inhibiting Serine Palmitoyltransferase.Nature communications · 2026Article
- Deletion of exon 2 in ALS-linkedLife science alliance · 2026Article
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- Characterization of novel and recurrentJournal of neuromuscular diseases · 2026Article
- A functional map of phosphoprotein phosphatase regulation identifies an evolutionarily conserved reductase for the catalytic metal ions.Nature communications · 2026Article
- Hypothalamic ceramide metabolism in obesity and dysregulation of glucose homeostasis.Reviews in endocrine & metabolic disorders · 2026Review
- ORMDL Proteins Turnover via Proteasome and Autophagy Is Cell-Type Dependent and Tied to Ceramide Homeostasis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- 1-deoxysphingolipids dysregulate membrane properties and cargo trafficking in the early secretory pathway.Cell chemical biology · 2026Article
- Effects of sphingolipid metabolism related genes-SPTLC1, ORMDL3, SPHK1 and S1PR3 polymorphisms on susceptibility to hashimoto's thyroiditis.Journal of endocrinological investigation · 2025Article
- The serine palmitoyl transferase of plant pathogenic fungi: a promising new target for the development of novel crop protection solutionsPest management science · 2025Article
- Intricate Regulation of Sphingolipid Biosynthesis: An In-Depth Look Into ORMDL-Mediated Regulation of Serine Palmitoyltransferase.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025Review
- Ceramide signaling in immunity: a molecular perspective.Lipids in health and disease · 2025Review
- Sphingolipid synthesis in tumor-associated macrophages confers immunotherapy resistance in hepatocellular carcinoma.Science advances · 2025Article
- Cysteine S-conjugate sulfoxide β-lyase activity for human ACCS.The FEBS journal · 2025Article
- Sphingolipid metabolites involved in the pathogenesis of atherosclerosis: perspectives on sphingolipids in atherosclerosis.Cellular & molecular biology letters · 2025Review
- Genetic and functional analyses of SPTLC1 in juvenile amyotrophic lateral sclerosis.Journal of neurology · 2024Article
- Regulation of cellular and systemic sphingolipid homeostasis.Nature reviews. Molecular cell biology · 2024Review
- SPTLC2 variants are associated with early-onset ALS and FTD due to aberrant sphingolipid synthesis.Annals of clinical and translational neurology · 2024Article
- Article
- Innovations in Antifungal Drug Discovery among Cell Envelope Synthesis Enzymes through Structural Insights.Journal of fungi (Basel, Switzerland) · 2024Review
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Authors and funding
12 authors.
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Abstract
Sphingolipids are essential lipids in eukaryotic membranes. In humans, the first and rate-limiting step of sphingolipid synthesis is catalyzed by the serine palmitoyltransferase holocomplex, which consists of catalytic components (SPTLC1 and SPTLC2) and regulatory components (ssSPTa and ORMDL3). However, the assembly, substrate processing and regulation of the complex are unclear. Here, we present 8 cryo-electron microscopy structures of the human serine palmitoyltransferase holocomplex in various functional states at resolutions of 2.6-3.4 Å. The structures reveal not only how catalytic components recognize the substrate, but also how regulatory components modulate the substrate-binding tunnel to control enzyme activity: ssSPTa engages SPTLC2 and shapes the tunnel to determine substrate specificity. ORMDL3 blocks the tunnel and competes with substrate binding through its amino terminus. These findings provide mechanistic insights into sphingolipid biogenesis governed by the serine palmitoyltransferase complex.
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