positive regulation of sphingolipid biosynthetic process / 3-keto-sphinganine metabolic process / negative regulation of sphingolipid biosynthetic process / multidimensional cell growth / serine palmitoyltransferase complex / intracellular sphingolipid homeostasis / : / serine C-palmitoyltransferase activity / serine C-palmitoyltransferase / ceramide metabolic process ...positive regulation of sphingolipid biosynthetic process / 3-keto-sphinganine metabolic process / negative regulation of sphingolipid biosynthetic process / multidimensional cell growth / serine palmitoyltransferase complex / intracellular sphingolipid homeostasis / : / serine C-palmitoyltransferase activity / serine C-palmitoyltransferase / ceramide metabolic process / regulation of programmed cell death / sphingosine biosynthetic process / embryo development ending in seed dormancy / sphingolipid biosynthetic process / ceramide biosynthetic process / response to unfolded protein / enzyme activator activity / Neutrophil degranulation / pyridoxal phosphate binding / endoplasmic reticulum membrane / endoplasmic reticulum / identical protein binding / membrane 類似検索 - 分子機能
ORMDL family / ORMDL family / Aminotransferase, class-II, pyridoxal-phosphate binding site / Aminotransferases class-II pyridoxal-phosphate attachment site. / Aminotransferase, class I/classII / Aminotransferase class I and II / Pyridoxal phosphate-dependent transferase, small domain / Pyridoxal phosphate-dependent transferase, major domain / Pyridoxal phosphate-dependent transferase 類似検索 - ドメイン・相同性
Serine palmitoyltransferase 1 / Serine palmitoyltransferase 2 / Protein ORM2 / Serine palmitoyltransferase-regulating protein TSC3 / Long chain base biosynthesis protein 1 類似検索 - 構成要素
ジャーナル: Cell Rep / 年: 2024 タイトル: Collaborative regulation of yeast SPT-Orm2 complex by phosphorylation and ceramide. 著者: 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 / ...著者: 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 / 要旨: The homeostatic regulation of serine palmitoyltransferase (SPT) activity in yeast involves N-terminal phosphorylation of Orm proteins, while higher eukaryotes lack these phosphorylation sites. ...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-terminal segments of Orm2. Moreover, we find that a phosphomimetic mutant of Orm2, positioned adjacent to its intramolecular β-sheet, destabilizes the inhibitory conformation of Orm2. Taken together, our findings suggest that both Orm dephosphorylation and ceramide binding are crucial for suppressing SPT activity in yeast. This highlights a distinctive regulatory mechanism in yeast involving the collaborative actions of phosphorylation and ceramide.