negative regulation of zinc ion transmembrane transport / Synthesis of PIPs at the early endosome membrane / Synthesis of PIPs at the late endosome membrane / Synthesis of PIPs at the Golgi membrane / Synthesis of PIPs at the plasma membrane / autophagosome organization / phosphatidylinositol-4-phosphate 3-kinase / Golgi Associated Vesicle Biogenesis / Clathrin-mediated endocytosis / phosphatidylinositol 3-kinase complex ...negative regulation of zinc ion transmembrane transport / Synthesis of PIPs at the early endosome membrane / Synthesis of PIPs at the late endosome membrane / Synthesis of PIPs at the Golgi membrane / Synthesis of PIPs at the plasma membrane / autophagosome organization / phosphatidylinositol-4-phosphate 3-kinase / Golgi Associated Vesicle Biogenesis / Clathrin-mediated endocytosis / phosphatidylinositol 3-kinase complex / 1-phosphatidylinositol-4-phosphate 3-kinase activity / 1-phosphatidylinositol-4,5-bisphosphate 3-kinase activity / phosphatidylinositol-4,5-bisphosphate 3-kinase / clathrin-coated vesicle / phosphatidylinositol 3-kinase / phosphatidylinositol-3-phosphate biosynthetic process / 1-phosphatidylinositol-3-kinase activity / clathrin binding / exocytosis / phosphatidylinositol-mediated signaling / phosphatidylinositol 3-kinase/protein kinase B signal transduction / cellular response to starvation / phosphatidylinositol binding / macroautophagy / trans-Golgi network / endocytosis / vesicle / ATP binding / nucleus / plasma membrane / cytoplasm 類似検索 - 分子機能
ジャーナル: Nat Struct Mol Biol / 年: 2022 タイトル: Structural basis of phosphatidylinositol 3-kinase C2α function. 著者: Wen-Ting Lo / Yingyi Zhang / Oscar Vadas / Yvette Roske / Federico Gulluni / Maria Chiara De Santis / Andreja Vujicic Zagar / Heike Stephanowitz / Emilio Hirsch / Fan Liu / Oliver Daumke / ...著者: Wen-Ting Lo / Yingyi Zhang / Oscar Vadas / Yvette Roske / Federico Gulluni / Maria Chiara De Santis / Andreja Vujicic Zagar / Heike Stephanowitz / Emilio Hirsch / Fan Liu / Oliver Daumke / Misha Kudryashev / Volker Haucke / 要旨: Phosphatidylinositol 3-kinase type 2α (PI3KC2α) is an essential member of the structurally unresolved class II PI3K family with crucial functions in lipid signaling, endocytosis, angiogenesis, ...Phosphatidylinositol 3-kinase type 2α (PI3KC2α) is an essential member of the structurally unresolved class II PI3K family with crucial functions in lipid signaling, endocytosis, angiogenesis, viral replication, platelet formation and a role in mitosis. The molecular basis of these activities of PI3KC2α is poorly understood. Here, we report high-resolution crystal structures as well as a 4.4-Å cryogenic-electron microscopic (cryo-EM) structure of PI3KC2α in active and inactive conformations. We unravel a coincident mechanism of lipid-induced activation of PI3KC2α at membranes that involves large-scale repositioning of its Ras-binding and lipid-binding distal Phox-homology and C-C2 domains, and can serve as a model for the entire class II PI3K family. Moreover, we describe a PI3KC2α-specific helical bundle domain that underlies its scaffolding function at the mitotic spindle. Our results advance our understanding of PI3K biology and pave the way for the development of specific inhibitors of class II PI3K function with wide applications in biomedicine.
解像度: 2.75→47.56 Å / Cor.coef. Fo:Fc: 0.935 / Cor.coef. Fo:Fc free: 0.907 / SU B: 24.606 / SU ML: 0.434 / 交差検証法: THROUGHOUT / σ(F): 0 / ESU R: 1.289 / ESU R Free: 0.392 / 立体化学のターゲット値: MAXIMUM LIKELIHOOD 詳細: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : REFINED INDIVIDUALLY
Rfactor
反射数
%反射
Selection details
Rfree
0.2891
1521
5 %
RANDOM
Rwork
0.2443
-
-
-
obs
0.2465
28894
98.82 %
-
溶媒の処理
イオンプローブ半径: 0.8 Å / 減衰半径: 0.8 Å / VDWプローブ半径: 1.2 Å / 溶媒モデル: MASK