7yj2
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | The entry | + | ==Cryo-EM structure of SPT-ORMDL3 (ORMDL3-N13A) complex== |
| + | <StructureSection load='7yj2' size='340' side='right'caption='[[7yj2]], [[Resolution|resolution]] 2.90Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[7yj2]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7YJ2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7YJ2 FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 2.9Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PLP:PYRIDOXAL-5-PHOSPHATE'>PLP</scene></td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7yj2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7yj2 OCA], [https://pdbe.org/7yj2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7yj2 RCSB], [https://www.ebi.ac.uk/pdbsum/7yj2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7yj2 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Disease == | ||
| + | [https://www.uniprot.org/uniprot/SPTC2_HUMAN SPTC2_HUMAN] Hereditary sensory and autonomic neuropathy type 1. The disease is caused by variants affecting the gene represented in this entry. SPTLC2 disease mutations cause a shift in the substrate specificity of SPT resulting in the alternative use of L-alanine and L-glycine over its canonical substrate L-serine. This leads to the production of 1-deoxysphingolipids that cannot be correctly metabolized (PubMed:23658386).<ref>PMID:23658386</ref> <ref>PMID:26573920</ref> | ||
| + | == 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> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == 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. | ||
| - | + | Ceramide sensing by human SPT-ORMDL complex for establishing sphingolipid homeostasis.,Xie T, Liu P, Wu X, Dong F, Zhang Z, Yue J, Mahawar U, Farooq F, Vohra H, Fang Q, Liu W, Wattenberg BW, Gong X Nat Commun. 2023 Jun 13;14(1):3475. doi: 10.1038/s41467-023-39274-y. PMID:37308477<ref>PMID:37308477</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 7yj2" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Gong X]] | ||
| + | [[Category: Liu P]] | ||
| + | [[Category: Xie T]] | ||
Revision as of 05:38, 5 July 2023
Cryo-EM structure of SPT-ORMDL3 (ORMDL3-N13A) complex
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Categories: Homo sapiens | Large Structures | Gong X | Liu P | Xie T
