8c82

From Proteopedia

(Difference between revisions)

Current revision

Cryo-EM structure of the yeast SPT-Orm1-Dimer complex

Structural highlights

8c82 is a 8 chain structure with sequence from Saccharomyces cerevisiae. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 3.4Å
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

LCB1_YEAST Component of serine palmitoyltransferase (SPT), which catalyzes the committed step in the synthesis of sphingolipids, the condensation of serine with palmitoyl CoA to form the long chain base 3-ketosphinganine.^[1] ^[2]

Publication Abstract from PubMed

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.

Structure of the ceramide-bound SPOTS complex.,Schafer JH, Korner C, Esch BM, Limar S, Parey K, Walter S, Januliene D, Moeller A, Frohlich F Nat Commun. 2023 Oct 4;14(1):6196. doi: 10.1038/s41467-023-41747-z. PMID:37794019^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Gable K, Han G, Monaghan E, Bacikova D, Natarajan M, Williams R, Dunn TM. Mutations in the yeast LCB1 and LCB2 genes, including those corresponding to the hereditary sensory neuropathy type I mutations, dominantly inactivate serine palmitoyltransferase. J Biol Chem. 2002 Mar 22;277(12):10194-200. PMID:11781309 doi:10.1074/jbc.M107873200
↑ Nagiec MM, Baltisberger JA, Wells GB, Lester RL, Dickson RC. The LCB2 gene of Saccharomyces and the related LCB1 gene encode subunits of serine palmitoyltransferase, the initial enzyme in sphingolipid synthesis. Proc Natl Acad Sci U S A. 1994 Aug 16;91(17):7899-902. PMID:8058731 doi:10.1073/pnas.91.17.7899
↑ Schäfer JH, Körner C, Esch BM, Limar S, Parey K, Walter S, Januliene D, Moeller A, Fröhlich F. Structure of the ceramide-bound SPOTS complex. Nat Commun. 2023 Oct 4;14(1):6196. PMID:37794019 doi:10.1038/s41467-023-41747-z

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/8c82"

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 8c82 is ON HOLD  until Paper Publication
+==Cryo-EM structure of the yeast SPT-Orm1-Dimer complex==
+<StructureSection load='8c82' size='340' side='right'caption='[[8c82]], [[Resolution|resolution]] 3.40&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[8c82]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8C82 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8C82 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]] 3.4&#8491;</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>, <scene name='pdbligand=Q7G:2-{[(4-O-alpha-D-glucopyranosyl-alpha-D-glucopyranosyl)oxy]methyl}-4-{[(3beta,9beta,14beta,17beta,25R)-spirost-5-en-3-yl]oxy}butyl+4-O-alpha-D-glucopyranosyl-alpha-D-glucopyranoside'>Q7G</scene>, <scene name='pdbligand=Z8A:N-[(2S,3S,4R)-1,3,4-trihydroxyoctadecan-2-yl]hexacosanamide'>Z8A</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=8c82 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8c82 OCA], [https://pdbe.org/8c82 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8c82 RCSB], [https://www.ebi.ac.uk/pdbsum/8c82 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8c82 ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/LCB1_YEAST LCB1_YEAST] Component of serine palmitoyltransferase (SPT), which catalyzes the committed step in the synthesis of sphingolipids, the condensation of serine with palmitoyl CoA to form the long chain base 3-ketosphinganine.<ref>PMID:11781309</ref> <ref>PMID:8058731</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+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.
-Authors:
+Structure of the ceramide-bound SPOTS complex.,Schafer JH, Korner C, Esch BM, Limar S, Parey K, Walter S, Januliene D, Moeller A, Frohlich F Nat Commun. 2023 Oct 4;14(1):6196. doi: 10.1038/s41467-023-41747-z. PMID:37794019<ref>PMID:37794019</ref>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 8c82" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Large Structures]]
+[[Category: Saccharomyces cerevisiae]]
+[[Category: Froehlich F]]
+[[Category: Januliene D]]
+[[Category: Koerner C]]
+[[Category: Moeller A]]
+[[Category: Parey K]]
+[[Category: Schaefer J]]

8c82

From Proteopedia

Current revision

Cryo-EM structure of the yeast SPT-Orm1-Dimer complex

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

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