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-Structure paper
タイトル | Collaborative regulation of yeast SPT-Orm2 complex by phosphorylation and ceramide. |
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ジャーナル・号・ページ | Cell Rep, Vol. 43, Issue 2, Page 113717, Year 2024 |
掲載日 | 2024年1月28日 |
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 / |
PubMed 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. |
リンク | Cell Rep / PubMed:38285738 |
手法 | EM (単粒子) |
解像度 | 3.1 Å |
構造データ | EMDB-35304, PDB-8iaj: EMDB-35306, PDB-8iak: EMDB-35310, PDB-8iam: |
化合物 | ChemComp-PLP: ChemComp-Z1T: |
由来 |
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キーワード | TRANSFERASE/INHIBITOR / ceramide / phosphorylation / TRANSFERASE-INHIBITOR COMPLEX |