ArticleNature structural & molecular biology2021
Structural insights into the assembly and substrate selectivity of human SPT-ORMDL3 complex.
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 56 papers.
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Who cites it
56 citing papers in PubMed, 95 citations in OpenAlex.
- Compound Z247611722 Exhibits Antifungal Activity by Inhibiting Serine Palmitoyltransferase.Nature communications · 2026Article
- Deletion of exon 2 in ALS-linkedLife science alliance · 2026Article
- Sphingolipids and Atherosclerosis.Current atherosclerosis reports · 2026Review
- 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
- Sex hormones influence ORMDL3 expression: Implications for sex-associated asthma phenotype.The Journal of allergy and clinical immunology · 2026Article
- Article
- Integrated transcriptomic and tissue-validation analyses identify palmitoylation-associated biomarkers linked to sphingolipid metabolism and immune remodeling in psoriasis.Frontiers in immunology · 2026Article
- Effects of sphingolipid metabolism related genes-SPTLC1, ORMDL3, SPHK1 and S1PR3 polymorphisms on susceptibility to hashimoto's thyroiditis.Journal of endocrinological investigation · 2025Article
- Orm2 promotes nitrogen-induced sphingolipid production and endocytosis via Orm1 phosphorylation.Journal of lipid research · 2025Article
- Resistant Potato Starch Supplementation Increases the Serum Levels of Choline and Sphingomyelins Without Affecting Trimethylamine Oxide Levels.Metabolites · 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
- SPTSSA facilitates gastric cancer progression with modulating PD-L1 in immunomicroenvironment through Wnt/β-catenin pathway.Cellular oncology (Dordrecht, Netherlands) · 2025Article
- Ceramide signaling in immunity: a molecular perspective.Lipids in health and disease · 2025Review
- Glia phagocytose neuronal sphingolipids to infiltrate developing synapses.bioRxiv : the preprint server for biology · 2025Article
- ORMDL3 restrains type I interferon signaling and anti-tumor immunity by promoting RIG-I degradation.eLife · 2025Article
- SPTLC2 drives an EGFR-FAK-HBEGF signaling axis to promote ovarian cancer progression.Oncogene · 2025Article
- Sphingolipid metabolites involved in the pathogenesis of atherosclerosis: perspectives on sphingolipids in atherosclerosis.Cellular & molecular biology letters · 2025Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Human serine palmitoyltransferase (SPT) complex catalyzes the initial and rate-limiting step in the de novo biosynthesis of all sphingolipids. ORMDLs regulate SPT function, with human ORMDL3 being related to asthma. Here we report three high-resolution cryo-EM structures: the human SPT complex, composed of SPTLC1, SPTLC2 and SPTssa; the SPT-ORMDL3 complex; and the SPT-ORMDL3 complex bound to two substrates, PLP-L-serine (PLS) and a non-reactive palmitoyl-CoA analogue. SPTLC1 and SPTLC2 form a dimer of heterodimers as the catalytic core. SPTssa participates in acyl-CoA coordination, thereby stimulating the SPT activity and regulating the substrate selectivity. ORMDL3 is located in the center of the complex, serving to stabilize the SPT assembly. Our structural and biochemical analyses provide a molecular basis for the assembly and substrate selectivity of the SPT and SPT-ORMDL3 complexes, and lay a foundation for mechanistic understanding of sphingolipid homeostasis and for related therapeutic drug development.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.