8QTN

Cryo-EM structure of the apo yeast Ceramide Synthase

Summary for 8QTN

• Entry DOI: 10.2210/pdb8qtn/pdb
• EMDB information: 18652
• Descriptor: Ceramide synthase LAG1, Ceramide synthase LAC1, Ceramide synthase subunit LIP1, ... (7 entities in total)
• Functional Keywords: ceramide synthase, membrane protein
• Biological source: Saccharomyces cerevisiae (brewer's yeast); More
• Total number of polymer chains: 4
• Total formula weight: 109747.24

Authors

Schaefer, J.,Clausmeyer, L.,Koerner, C.,Moeller, A.,Froehlich, F. (deposition date: 2023-10-12, release date: 2024-10-23, Last modification date: 2025-03-26)

Primary citation

Schafer, J.H.,Clausmeyer, L.,Korner, C.,Esch, B.M.,Wolf, V.N.,Sapia, J.,Ahmed, Y.,Walter, S.,Vanni, S.,Januliene, D.,Moeller, A.,Frohlich, F.
Structure of the yeast ceramide synthase.
Nat.Struct.Mol.Biol., 32:441-449, 2025

PubMed Abstract: 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.

PubMed: 39528796
DOI: 10.1038/s41594-024-01415-2

Experimental method

ELECTRON MICROSCOPY (3 Å)