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Collaborative regulation of yeast SPT-Orm2 complex by phosphorylation and ceramide

Cell Rep .. 2024-01; 
Tian Xie , Feitong Dong , Gongshe Han , Xinyue Wu , Peng Liu , Zike Zhang , Jianlong Zhong , Somashekarappa Niranjanakumari , Kenneth Gable , Sita D Gupta , Wenchen Liu , Peter J Harrison , Dominic J Campopiano , Teresa M Dunn , Xin Gong
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摘要

The homeostatic regulation of serine palmitoyltransferase (SPT) activity in yeast involves N-terminal phosphorylation of Orm proteins, while higher eukaryotes lack these phosphorylation sites. Although recent studies have indicated a conserved ceramide-mediated feedback inhibition of the SPT-ORM/ORMDL complex in higher eukaryotes, its conservation and relationship with phosphorylation regulation in yeast remain unclear. Here, we determine the structure of the yeast SPT-Orm2 complex in a dephosphomimetic state and identify an evolutionarily conserved ceramide-sensing site. Ceramide stabilizes the dephosphomimetic Orm2 in an inhibitory conformation, facilitated by an intramolecular β-sheet between the N- and C-t... More

关键词

CP: Metabolism; CP: Molecular biology.