7yj2
From Proteopedia
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== Function == | == Function == | ||
[https://www.uniprot.org/uniprot/SPTC2_HUMAN SPTC2_HUMAN] Serine palmitoyltransferase (SPT). The heterodimer formed with LCB1/SPTLC1 constitutes the catalytic core. The composition of the serine palmitoyltransferase (SPT) complex determines the substrate preference. The SPTLC1-SPTLC2-SPTSSA complex shows a strong preference for C16-CoA substrate, while the SPTLC1-SPTLC2-SPTSSB complex displays a preference for C18-CoA substrate. Plays an important role in de novo sphyngolipid biosynthesis which is crucial for adipogenesis (By similarity).[UniProtKB:P97363]<ref>PMID:19416851</ref> <ref>PMID:19648650</ref> <ref>PMID:20920666</ref> | [https://www.uniprot.org/uniprot/SPTC2_HUMAN SPTC2_HUMAN] Serine palmitoyltransferase (SPT). The heterodimer formed with LCB1/SPTLC1 constitutes the catalytic core. The composition of the serine palmitoyltransferase (SPT) complex determines the substrate preference. The SPTLC1-SPTLC2-SPTSSA complex shows a strong preference for C16-CoA substrate, while the SPTLC1-SPTLC2-SPTSSB complex displays a preference for C18-CoA substrate. Plays an important role in de novo sphyngolipid biosynthesis which is crucial for adipogenesis (By similarity).[UniProtKB:P97363]<ref>PMID:19416851</ref> <ref>PMID:19648650</ref> <ref>PMID:20920666</ref> | ||
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| - | == Publication Abstract from PubMed == | ||
| - | The ORM/ORMDL family proteins function as regulatory subunits of the serine palmitoyltransferase (SPT) complex, which is the initiating and rate-limiting enzyme in sphingolipid biosynthesis. This complex is tightly regulated by cellular sphingolipid levels, but the sphingolipid sensing mechanism is unknown. Here we show that purified human SPT-ORMDL complexes are inhibited by the central sphingolipid metabolite ceramide. We have solved the cryo-EM structure of the SPT-ORMDL3 complex in a ceramide-bound state. Structure-guided mutational analyses reveal the essential function of this ceramide binding site for the suppression of SPT activity. Structural studies indicate that ceramide can induce and lock the N-terminus of ORMDL3 into an inhibitory conformation. Furthermore, we demonstrate that childhood amyotrophic lateral sclerosis (ALS) variants in the SPTLC1 subunit cause impaired ceramide sensing in the SPT-ORMDL3 mutants. Our work elucidates the molecular basis of ceramide sensing by the SPT-ORMDL complex for establishing sphingolipid homeostasis and indicates an important role of impaired ceramide sensing in disease development. | ||
| - | + | ==See Also== | |
| - | + | *[[Serine palmitoyltransferase 3D structures|Serine palmitoyltransferase 3D structures]] | |
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== References == | == References == | ||
<references/> | <references/> | ||
Revision as of 09:30, 20 March 2024
Cryo-EM structure of SPT-ORMDL3 (ORMDL3-N13A) complex
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Categories: Homo sapiens | Large Structures | Gong X | Liu P | Xie T
