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	Structures of the PI3Kα/KRas complex on lipid bilayers reveal molecular mechanisms of PI3Kα activation.
ジャーナル・号・ページ	Mol Cell, Vol. 86, Issue 14, Page 2858-22870.e6, Year 2026
掲載日	2026年7月16日
著者	Hayarpi Torosyan / Michael D Paul / Brigitte G Meyer / Allison Maker / Natalia Jura / Kliment A Verba /
PubMed 要旨	PI3Kα is a potent oncogene that converts PIP2 to PIP3 at the plasma membrane upon activation by receptor tyrosine kinases and Ras. To understand the molecular mechanism of PI3Kα activation, we used ...PI3Kα is a potent oncogene that converts PIP2 to PIP3 at the plasma membrane upon activation by receptor tyrosine kinases and Ras. To understand the molecular mechanism of PI3Kα activation, we used cryo-electron microscopy to visualize the conformational states that underlie its transition to an active signaling complex. Here, we present structures of the PI3Kα/KRas complex embedded in lipid nanodiscs, revealing a rich ensemble of PI3Kα conformations that capture the progressive release of key inhibitory domains from the PI3Kα catalytic core. PIP2 triggers significant restructuring of active site regulatory motifs while an activating phosphopeptide induces dimerization of the PI3Kα/KRas complex through a p110α catalytic subunit-mediated interface that is sterically occluded in autoinhibited PI3Kα. In cells, dimeric PI3Kα amplifies Akt signaling in response to growth factor stimulation. Collectively, these structures map the conformational landscape of PI3Kα activation and reveal previously unexplored interfaces for potential therapeutic targeting.
リンク	Mol Cell / PubMed:42349404 / PubMed Central
手法	EM (単粒子)
解像度	2.61 - 10.0 Å
構造データ	49451 9ni3 EMDB-49451, PDB-9ni3: Cryo-EM structure of the PI3K alpha/KRas complex on POPC/POPS/PIP2 nanodiscs 手法: EM (単粒子) / 解像度: 2.82 Å 49452 9ni4 EMDB-49452, PDB-9ni4: Cryo-EM structure of the PI3K alpha/KRas/HER3 phosphopeptide complex dimer on POPC/POPS/PIP2 nanodiscs 手法: EM (単粒子) / 解像度: 2.61 Å 49453 9ni5 EMDB-49453, PDB-9ni5: Cryo-EM structure of the PI3K alpha/KRas/HER3 phosphopeptide complex on POPC/POPS/PIP2 nanodiscs 手法: EM (単粒子) / 解像度: 2.89 Å 49454 9ni6 EMDB-49454, PDB-9ni6: Cryo-EM structure of the Class 1 PI3K alpha/KRas complex on POPC/POPS nanodiscs 手法: EM (単粒子) / 解像度: 3.01 Å 49455 9ni7 EMDB-49455, PDB-9ni7: Cryo-EM structure of the Class 3 PI3K alpha/KRas complex on POPC/POPS nanodiscs 手法: EM (単粒子) / 解像度: 3.05 Å 49456 9ni8 EMDB-49456, PDB-9ni8: Cryo-EM structure of the Class 2 PI3K alpha/KRas complex on POPC/POPS nanodiscs 手法: EM (単粒子) / 解像度: 3.23 Å 49458 9nid EMDB-49458, PDB-9nid: Cryo-EM structure of the PI3K alpha/KRas/HER3 phosphopeptide complex dimer on POPC/POPS/PIP2 nanodiscs low-pass filtered to 5 angstroms 手法: EM (単粒子) / 解像度: 5.0 Å 49459 9nie EMDB-49459, PDB-9nie: Cryo-EM structure of the PI3K alpha/KRas/HER3 phosphopeptide complex on POPC/POPS/PIP2 nanodiscs low-pass filtered to 5 angstroms 手法: EM (単粒子) / 解像度: 5.0 Å 49460 9nif EMDB-49460, PDB-9nif: Cryo-EM structure of the PI3K alpha/KRas complex on POPC/POPS/PIP2 nanodiscs low-pass filtered to 5 angstroms 手法: EM (単粒子) / 解像度: 5.0 Å 49519 9nlc EMDB-49519, PDB-9nlc: Cryo-EM structure of the Class 1 PI3K alpha/KRas complex on POPC/POPS nanodiscs low-pass filtered to 10 angstroms 手法: EM (単粒子) / 解像度: 10.0 Å
化合物	ChemComp-PBU: (2R)-3-{[(R)-HYDROXY{[(1R,2R,3S,4R,5R,6S)-2,3,6-TRIHYDROXY-4,5-BIS(PHOSPHONOOXY)CYCLOHEXYL]OXY}PHOSPHORYL]OXY}PROPANE-1 PDB-1azd: CONCANAVALIN FROM CANAVALIA BRASILIENSIS ChemComp-MG: Unknown entry ChemComp-GNP: PHOSPHOAMINOPHOSPHONIC ACID-GUANYLATE ESTER / GppNHp, GMPPNP, エネルギー貯蔵分子類似体*YM
由来	homo sapiens (ヒト)
キーワード	ONCOPROTEIN/Hydrolase / lipid kinase / GTPase / ONCOPROTEIN / ONCOPROTEIN-Hydrolase complex / Transferase/Hydrolase / Transferase-Hydrolase complex