sphinganine biosynthetic process / regulation of fat cell apoptotic process / serine palmitoyltransferase complex / sphingomyelin biosynthetic process / : / serine C-palmitoyltransferase activity / serine C-palmitoyltransferase / sphingosine biosynthetic process / sphingolipid biosynthetic process / Sphingolipid de novo biosynthesis ...sphinganine biosynthetic process / regulation of fat cell apoptotic process / serine palmitoyltransferase complex / sphingomyelin biosynthetic process / : / serine C-palmitoyltransferase activity / serine C-palmitoyltransferase / sphingosine biosynthetic process / sphingolipid biosynthetic process / Sphingolipid de novo biosynthesis / sphingolipid metabolic process / ceramide biosynthetic process / positive regulation of lipophagy / adipose tissue development / protein localization / pyridoxal phosphate binding / endoplasmic reticulum membrane / endoplasmic reticulum 類似検索 - 分子機能
: / Small subunit of serine palmitoyltransferase-like / Small subunit of serine palmitoyltransferase-like / : / 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 / Serine palmitoyltransferase small subunit A 類似検索 - 構成要素
ジャーナル: Nat Struct Mol Biol / 年: 2021 タイトル: Structural insights into the regulation of human serine palmitoyltransferase complexes. 著者: Yingdi Wang / Yiming Niu / Zhe Zhang / Kenneth Gable / Sita D Gupta / Niranjanakumari Somashekarappa / Gongshe Han / Hongtu Zhao / Alexander G Myasnikov / Ravi C Kalathur / Teresa M Dunn / Chia-Hsueh Lee / 要旨: 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 ...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.