7K0O

Human serine palmitoyltransferase complex SPTLC1/SPLTC2/ssSPTa/ORMDL3, class 3

7K0O の概要

• エントリーDOI: 10.2210/pdb7k0o/pdb
• EMDBエントリー: 22605
• 分子名称: Serine palmitoyltransferase 1, Serine palmitoyltransferase 2, Serine palmitoyltransferase small subunit A, ... (6 entities in total)
• 機能のキーワード: sphingolipid, membrane protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 288899.92

構造登録者

Wang, Y.,Niu, Y.,Zhang, Z.,Zhao, H.,Myasnikov, A.,Kalathur, R.,Lee, C.H. (登録日: 2020-09-04, 公開日: 2021-02-24, 最終更新日: 2021-03-24)

主引用文献

Wang, Y.,Niu, Y.,Zhang, Z.,Gable, K.,Gupta, S.D.,Somashekarappa, N.,Han, G.,Zhao, H.,Myasnikov, A.G.,Kalathur, R.C.,Dunn, T.M.,Lee, C.H.
Structural insights into the regulation of human serine palmitoyltransferase complexes.
Nat.Struct.Mol.Biol., 28:240-248, 2021

PubMed Abstract: Sphingolipids are essential lipids in eukaryotic membranes. In humans, the first and rate-limiting step of sphingolipid synthesis is catalyzed by the serine palmitoyltransferase holocomplex, which consists of catalytic components (SPTLC1 and SPTLC2) and regulatory components (ssSPTa and ORMDL3). However, the assembly, substrate processing and regulation of the complex are unclear. Here, we present 8 cryo-electron microscopy structures of the human serine palmitoyltransferase holocomplex in various functional states at resolutions of 2.6-3.4 Å. The structures reveal not only how catalytic components recognize the substrate, but also how regulatory components modulate the substrate-binding tunnel to control enzyme activity: ssSPTa engages SPTLC2 and shapes the tunnel to determine substrate specificity. ORMDL3 blocks the tunnel and competes with substrate binding through its amino terminus. These findings provide mechanistic insights into sphingolipid biogenesis governed by the serine palmitoyltransferase complex.

PubMed: 33558761
DOI: 10.1038/s41594-020-00551-9

実験手法

ELECTRON MICROSCOPY (3.1 Å)