8izd

From Proteopedia

(Difference between revisions)

Revision as of 11:44, 13 December 2023

Cryo-EM structure of the C26-CoA-bound Lac1-Lip1 complex

Structural highlights

8izd is a 4 chain structure with sequence from Saccharomyces cerevisiae S288C. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 3.09Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

LAC1_YEAST Component of the ceramide synthase complex that catalyzes the transfer of the acyl chain from acyl-CoA to a sphingoid base, with high selectivity toward hexacosanoyl-CoA (C26:0-CoA) (PubMed:15692566, PubMed:11694577). N-acylates sphinganine and phytosphingosine bases to form dihydroceramides and phytoceramides, respectively (PubMed:15692566, PubMed:11694577). Redundant with LAG1. Facilitates ER-to-Golgi transport of GPI-anchored proteins.^[1] ^[2] ^[3] ^[4]

Publication Abstract from PubMed

Ceramide synthases (CerS) catalyze ceramide formation via N-acylation of a sphingoid base with a fatty acyl-CoA and are attractive drug targets for treating numerous metabolic diseases and cancers. Here, we present the cryo-EM structure of a yeast CerS complex, consisting of a catalytic Lac1 subunit and a regulatory Lip1 subunit, in complex with C26-CoA substrate. The CerS holoenzyme exists as a dimer of Lac1-Lip1 heterodimers. Lac1 contains a hydrophilic reaction chamber and a hydrophobic tunnel for binding the CoA moiety and C26-acyl chain of C26-CoA, respectively. Lip1 interacts with both the transmembrane region and the last luminal loop of Lac1 to maintain the proper acyl chain binding tunnel. A lateral opening on Lac1 serves as a potential entrance for the sphingoid base substrate. Our findings provide a template for understanding the working mechanism of eukaryotic ceramide synthases and may facilitate the development of therapeutic CerS modulators.

Structure and mechanism of a eukaryotic ceramide synthase complex.,Xie T, Fang Q, Zhang Z, Wang Y, Dong F, Gong X EMBO J. 2023 Dec 11;42(24):e114889. doi: 10.15252/embj.2023114889. Epub 2023 Nov , 13. PMID:37953642^[5]

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

References

↑ Barz WP, Walter P. Two endoplasmic reticulum (ER) membrane proteins that facilitate ER-to-Golgi transport of glycosylphosphatidylinositol-anchored proteins. Mol Biol Cell. 1999 Apr;10(4):1043-59. PMID:10198056 doi:10.1091/mbc.10.4.1043
↑ Guillas I, Kirchman PA, Chuard R, Pfefferli M, Jiang JC, Jazwinski SM, Conzelmann A. C26-CoA-dependent ceramide synthesis of Saccharomyces cerevisiae is operated by Lag1p and Lac1p. EMBO J. 2001 Jun 1;20(11):2655-65. PMID:11387200 doi:10.1093/emboj/20.11.2655
↑ Schorling S, Vallée B, Barz WP, Riezman H, Oesterhelt D. Lag1p and Lac1p are essential for the Acyl-CoA-dependent ceramide synthase reaction in Saccharomyces cerevisae. Mol Biol Cell. 2001 Nov;12(11):3417-27. PMID:11694577 doi:10.1091/mbc.12.11.3417
↑ Vallée B, Riezman H. Lip1p: a novel subunit of acyl-CoA ceramide synthase. EMBO J. 2005 Feb 23;24(4):730-41. PMID:15692566 doi:10.1038/sj.emboj.7600562
↑ Xie T, Fang Q, Zhang Z, Wang Y, Dong F, Gong X. Structure and mechanism of a eukaryotic ceramide synthase complex. EMBO J. 2023 Dec 11;42(24):e114889. PMID:37953642 doi:10.15252/embj.2023114889

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/8izd"

Categories: Large Structures | Saccharomyces cerevisiae S288C | Fang Q | Gong X | Xie T

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 8izd is ON HOLD  until 2025-04-07
+==Cryo-EM structure of the C26-CoA-bound Lac1-Lip1 complex==
+<StructureSection load='8izd' size='340' side='right'caption='[[8izd]], [[Resolution|resolution]] 3.09&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[8izd]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae_S288C Saccharomyces cerevisiae S288C]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8IZD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8IZD 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]] 3.09&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6PL:(4S,7R)-4-HYDROXY-N,N,N-TRIMETHYL-9-OXO-7-[(PALMITOYLOXY)METHYL]-3,5,8-TRIOXA-4-PHOSPHAHEXACOSAN-1-AMINIUM+4-OXIDE'>6PL</scene>, <scene name='pdbligand=9NY:Hexacosanoyl-CoA'>9NY</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=8izd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8izd OCA], [https://pdbe.org/8izd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8izd RCSB], [https://www.ebi.ac.uk/pdbsum/8izd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8izd ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/LAC1_YEAST LAC1_YEAST] Component of the ceramide synthase complex that catalyzes the transfer of the acyl chain from acyl-CoA to a sphingoid base, with high selectivity toward hexacosanoyl-CoA (C26:0-CoA) (PubMed:15692566, PubMed:11694577). N-acylates sphinganine and phytosphingosine bases to form dihydroceramides and phytoceramides, respectively (PubMed:15692566, PubMed:11694577). Redundant with LAG1. Facilitates ER-to-Golgi transport of GPI-anchored proteins.<ref>PMID:10198056</ref> <ref>PMID:11387200</ref> <ref>PMID:11694577</ref> <ref>PMID:15692566</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Ceramide synthases (CerS) catalyze ceramide formation via N-acylation of a sphingoid base with a fatty acyl-CoA and are attractive drug targets for treating numerous metabolic diseases and cancers. Here, we present the cryo-EM structure of a yeast CerS complex, consisting of a catalytic Lac1 subunit and a regulatory Lip1 subunit, in complex with C26-CoA substrate. The CerS holoenzyme exists as a dimer of Lac1-Lip1 heterodimers. Lac1 contains a hydrophilic reaction chamber and a hydrophobic tunnel for binding the CoA moiety and C26-acyl chain of C26-CoA, respectively. Lip1 interacts with both the transmembrane region and the last luminal loop of Lac1 to maintain the proper acyl chain binding tunnel. A lateral opening on Lac1 serves as a potential entrance for the sphingoid base substrate. Our findings provide a template for understanding the working mechanism of eukaryotic ceramide synthases and may facilitate the development of therapeutic CerS modulators.
-Authors:
+Structure and mechanism of a eukaryotic ceramide synthase complex.,Xie T, Fang Q, Zhang Z, Wang Y, Dong F, Gong X EMBO J. 2023 Dec 11;42(24):e114889. doi: 10.15252/embj.2023114889. Epub 2023 Nov , 13. PMID:37953642<ref>PMID:37953642</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 8izd" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Large Structures]]
+[[Category: Saccharomyces cerevisiae S288C]]
+[[Category: Fang Q]]
+[[Category: Gong X]]
+[[Category: Xie T]]

8izd

From Proteopedia

Revision as of 11:44, 13 December 2023

Cryo-EM structure of the C26-CoA-bound Lac1-Lip1 complex

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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