EMDB/PDB/SASBDBから引用されている文献のデータベース

キーワード
構造解析手法	All X線回折 NMR 電子顕微鏡小角散乱中性子線回折線維回折粉末回折赤外分光 EPR FRET 理論モデルハイブリッド
著者・登録者
ジャーナル
IF	>30 >20 >10 >5 all

タイトル	Structural pathway for PI3-kinase regulation by VPS15 in autophagy.
ジャーナル・号・ページ	Science, Vol. 388, Issue 6743, Page eadl3787, Year 2025
掲載日	2025年4月11日
著者	Annan S I Cook / Minghao Chen / Thanh N Nguyen / Ainara Claveras Cabezudo / Grace Khuu / Shanlin Rao / Samantha N Garcia / Mingxuan Yang / Anthony T Iavarone / Xuefeng Ren / Michael Lazarou / Gerhard Hummer / James H Hurley /
PubMed 要旨	The class III phosphatidylinositol-3 kinase complexes I and II (PI3KC3-C1 and PI3KC3-C2) have vital roles in macroautophagy and endosomal maturation, respectively. We elucidated a structural pathway ...The class III phosphatidylinositol-3 kinase complexes I and II (PI3KC3-C1 and PI3KC3-C2) have vital roles in macroautophagy and endosomal maturation, respectively. We elucidated a structural pathway of enzyme activation through cryo-electron microscopy analysis of PI3KC3-C1. The inactive conformation of the VPS15 pseudokinase stabilizes the inactive conformation, sequestering its -myristate in the N-lobe of the pseudokinase. Upon activation, the myristate is liberated such that the VPS34 lipid kinase catalyzes phosphatidylinositol-3 phosphate production on membranes. The VPS15 pseudokinase domain binds tightly to guanosine triphosphate and stabilizes a web of interactions to autoinhibit the cytosolic complex and promote activation upon membrane binding. These findings show in atomistic detail how the VPS34 lipid kinase is activated in the context of a complete PI3K complex.
リンク	Science / PubMed:39913640 / PubMed Central
手法	EM (単粒子)
解像度	2.62 - 5.0 Å
構造データ	EMDB-48230: PI3KC3-C1 bound to RAB1A, no VPS34 Kinase domain 手法: EM (単粒子) / 解像度: 2.73 Å EMDB-48231: Local Refinement of VPS15 pseudokinase domain and helical repeats 手法: EM (単粒子) / 解像度: 2.67 Å EMDB-48232: PI3KC3-C1 Bound to RAB1A local refinement of RAB1A/VPS34 interface 手法: EM (単粒子) / 解像度: 2.68 Å EMDB-48233: PI3KC3-C1 bound to RAB1A. Local refinement of Bara like domains of BECN1 and ATG14, and VPS15 WD40 domain 手法: EM (単粒子) / 解像度: 2.62 Å EMDB-48257: PI3KC3-C1 bound to RAB1A in the inactive state. Consensus refinement 手法: EM (単粒子) / 解像度: 3.1 Å EMDB-48258: PI3KC3C1 bound to RAB1A, Inactive state, VPS34 kinase domain local refinement 手法: EM (単粒子) / 解像度: 3.1 Å EMDB-48259: PI3KC3-C1 bound to RAB1A. Consensus inactive state refinement of particle subset with strongest kinase domain density 手法: EM (単粒子) / 解像度: 3.3 Å EMDB-48260: PI3KC3-C1 bound to RAB1A. Local refinement of VPS34KD in the inactive state, particle subset 手法: EM (単粒子) / 解像度: 3.3 Å EMDB-48272: PI3KC3-C1 bound to RAB1A. VPS34 kinase domain in the active conformation, consensus reconstruction 手法: EM (単粒子) / 解像度: 5.0 Å 48276 9mhf EMDB-48276, PDB-9mhf: Cryo-EM reconstruction of PI3KC3-C1 in complex with Human RAB1A(Q70L) 手法: EM (単粒子) / 解像度: 2.73 Å 48277 9mhg EMDB-48277, PDB-9mhg: Cryo EM reconstruction of PI3KC3-C1 in complex with Human RAB1A(Q70L), VPS34 kinase domain in the inactive conformation 手法: EM (単粒子) / 解像度: 3.2 Å 48278 9mhh EMDB-48278, PDB-9mhh: PI3KC3-C1 in complex with RAB1A. VPS34 kinase domain active conformation 手法: EM (単粒子) / 解像度: 4.5 Å
化合物	ChemComp-GTP: GUANOSINE-5'-TRIPHOSPHATE / GTP / GTP, エネルギー貯蔵分子YM ChemComp-MG: Unknown entry / マグネシウムジカチオン ChemComp-MYR: MYRISTIC ACID / ミリスチン酸 ChemComp-HOH*: WATER
由来	homo sapiens (ヒト)
キーワード	SIGNALING PROTEIN / Complex / GTPase / GTP-binding / Autophagy / Kinase / Lipid Kinase