Jan-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
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引用次数: 0
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. Using cryo-electron microscopy, Schäfer et al. solved the structure of the yeast ceramide synthase complex, consisting of Lip1, Lag1 and Lac1 subunits. They found that fumonisin B1 binds competitively at a key site, suggesting a mechanism for ceramide synthesis.
期刊介绍:
Nature Structural & Molecular Biology is a comprehensive platform that combines structural and molecular research. Our journal focuses on exploring the functional and mechanistic aspects of biological processes, emphasizing how molecular components collaborate to achieve a particular function. While structural data can shed light on these insights, our publication does not require them as a prerequisite.