8QOF

Cryo-EM structure of the yeast SPT-Orm2-Dimer complex

8QOF の概要

• エントリーDOI: 10.2210/pdb8qof/pdb
• EMDBエントリー: 18536
• 分子名称: Serine palmitoyltransferase 1, Serine palmitoyltransferase-regulating protein TSC3, ORM2 isoform 1, ... (7 entities in total)
• 機能のキーワード: serine-palmitoyl-transferase, transferase
• 由来する生物種: Saccharomyces cerevisiae (baker's yeast); 詳細
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 329437.45

構造登録者

Schaefer, J.,Koerner, C.,Moeller, A.,Froehlich, F. (登録日: 2023-09-28, 公開日: 2024-09-04)

主引用文献

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

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: 39167489
DOI: 10.1016/j.celrep.2024.114627

実験手法

ELECTRON MICROSCOPY (3.3 Å)