8QOF
Cryo-EM structure of the yeast SPT-Orm2-Dimer complex
Summary for 8QOF
| Entry DOI | 10.2210/pdb8qof/pdb |
| EMDB information | 18536 |
| Descriptor | Serine palmitoyltransferase 1, Serine palmitoyltransferase-regulating protein TSC3, ORM2 isoform 1, ... (7 entities in total) |
| Functional Keywords | serine-palmitoyl-transferase, transferase |
| Biological source | Saccharomyces cerevisiae (baker's yeast) More |
| Total number of polymer chains | 8 |
| Total formula weight | 329437.45 |
| Authors | Schaefer, J.,Koerner, C.,Moeller, A.,Froehlich, F. (deposition date: 2023-09-28, release date: 2024-09-04) |
| Primary citation | Korner, C.,Schafer, J.H.,Esch, B.M.,Parey, K.,Walter, S.,Teis, D.,Januliene, D.,Schmidt, O.,Moeller, A.,Frohlich, F. The structure of the Orm2-containing serine palmitoyltransferase complex reveals distinct inhibitory potentials of yeast Orm proteins. Cell Rep, 43:114627-114627, 2024 Cited by PubMed Abstract: Sphingolipid levels are crucial determinants of neurodegenerative disorders and therefore require tight regulation. The Orm protein family and ceramides inhibit the rate-limiting step of sphingolipid biosynthesis-the condensation of L-serine and palmitoyl-coenzyme A (CoA). The yeast isoforms Orm1 and Orm2 form a complex with the serine palmitoyltransferase (SPT). While Orm1 and Orm2 have highly similar sequences, they are differentially regulated, though the mechanistic details remain elusive. Here, we determine the cryoelectron microscopy structure of the SPT complex containing Orm2. Complementary in vitro activity assays and genetic experiments with targeted lipidomics demonstrate a lower activity of the SPT-Orm2 complex than the SPT-Orm1 complex. Our results suggest a higher inhibitory potential of Orm2, despite the similar structures of the Orm1- and Orm2-containing complexes. The high conservation of SPT from yeast to man implies different regulatory capacities for the three human ORMDL isoforms, which might be key for understanding their role in sphingolipid-mediated neurodegenerative disorders. PubMed: 39167489DOI: 10.1016/j.celrep.2024.114627 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.3 Å) |
Structure validation
Download full validation report
