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TitleStructure of the yeast ceramide synthase.
Journal, issue, pagesNat Struct Mol Biol, Year 2024
Publish dateNov 11, 2024
AuthorsJan-Hannes Schäfer / Lena Clausmeyer / Carolin Körner / Bianca M Esch / Verena N Wolf / Jennifer Sapia / Yara Ahmed / Stefan Walter / Stefano Vanni / Dovile Januliene / Arne Moeller / Florian Fröhlich /
PubMed AbstractCeramides are essential lipids involved in forming complex sphingolipids and acting as signaling molecules. They result from the N-acylation of a sphingoid base and a CoA-activated fatty acid, a ...Ceramides are essential lipids involved in forming complex sphingolipids and acting as signaling molecules. They result from the N-acylation of a sphingoid base and a CoA-activated fatty acid, a reaction catalyzed by the ceramide synthase (CerS) family of enzymes. Yet, the precise structural details and catalytic mechanisms of CerSs have remained elusive. Here we used cryo-electron microscopy single-particle analysis to unravel the structure of the yeast CerS complex in both an active and a fumonisin B1-inhibited state. Our results reveal the complex's architecture as a dimer of Lip1 subunits bound to the catalytic subunits Lag1 and Lac1. Each catalytic subunit forms a hydrophobic crevice connecting the cytosolic site with the intermembrane space. The active site, located centrally in the tunnel, was resolved in a substrate preloaded state, representing one intermediate in ceramide synthesis. Our data provide evidence for competitive binding of fumonisin B1 to the acyl-CoA-binding tunnel.
External linksNat Struct Mol Biol / PubMed:39528796
MethodsEM (single particle)
Resolution3.0 - 3.2 Å
Structure data

18652

8qtn

EMDB-18652, PDB-8qtn:
Cryo-EM structure of the apo yeast Ceramide Synthase
Method: EM (single particle) / Resolution: 3.0 Å

18653

8qtr

EMDB-18653, PDB-8qtr:
Cryo-EM structure of the FB-bound yeast Ceramide Synthase
Method: EM (single particle) / Resolution: 3.2 Å

Chemicals

ChemComp-3PE:
1,2-Distearoyl-sn-glycerophosphoethanolamine / phospholipid*YM

ChemComp-7PO:
hexacosanoic acid


ChemComp, No image

ChemComp-PIJ:
Unknown entry

ChemComp-NH4:
AMMONIUM ION


ChemComp, No image

ChemComp-WXE:
Unknown entry

Source
  • saccharomyces cerevisiae (brewer's yeast)
KeywordsMEMBRANE PROTEIN / Ceramide Synthase

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