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 basis for mTORC1 activation on the lysosomal membrane.
ジャーナル・号・ページ	Nature, Vol. 647, Issue 8089, Page 536-543, Year 2025
掲載日	2025年9月17日
著者	Zhicheng Cui / Alessandra Esposito / Gennaro Napolitano / Andrea Ballabio / James H Hurley /
PubMed 要旨	The mechanistic target of rapamycin complex 1 (mTORC1) integrates growth factor (GF) and nutrient signals to stimulate anabolic processes connected to cell growth and inhibit catabolic processes such ...The mechanistic target of rapamycin complex 1 (mTORC1) integrates growth factor (GF) and nutrient signals to stimulate anabolic processes connected to cell growth and inhibit catabolic processes such as autophagy. GF signalling through the tuberous sclerosis complex regulates the lysosomally localized small GTPase RAS homologue enriched in brain (RHEB). Direct binding of RHEB-GTP to the mTOR kinase subunit of mTORC1 allosterically activates the kinase by inducing a large-scale conformational change. Here we reconstituted mTORC1 activation on membranes by RHEB, RAGs and Ragulator. Cryo-electron microscopy showed that RAPTOR and mTOR interact directly with the membrane. Full engagement of the membrane anchors is required for optimal alignment of the catalytic residues in the mTOR kinase active site. Converging signals from GFs and nutrients drive mTORC1 recruitment to and activation on lysosomal membrane in a four-step process, consisting of (1) RAG-Ragulator-driven recruitment to within ~100 Å of the lysosomal membrane; (2) RHEB-driven recruitment to within ~40 Å; (3) RAPTOR-membrane engagement and intermediate enzyme activation; and (4) mTOR-membrane engagement and full enzyme activation. RHEB and membrane engagement combined leads to full catalytic activation and structurally explains GF and nutrient signal integration at the lysosome.
リンク	Nature / PubMed:40963021 / PubMed Central
手法	EM (単粒子)
解像度	2.98 - 3.98 Å
構造データ	47932 9ed4 EMDB-47932, PDB-9ed4: A composite map of mTORC1-Rag-Ragultor-4EBP1 on membrane 手法: EM (単粒子) / 解像度: 3.23 Å 47933 9ed6 EMDB-47933, PDB-9ed6: CryoEM map of the mLST8-Rag-Ragultor subcomplex 手法: EM (単粒子) / 解像度: 3.98 Å EMDB-47934: mTORC1-Rag-Ragulator-4EBP1 on membrane with two extra Rag-Ragulator 手法: EM (単粒子) / 解像度: 3.81 Å EMDB-47935: mTORC1-Rag-Ragulator-4EBP1 on membrane with one extra Rag-Ragulator 手法: EM (単粒子) / 解像度: 3.47 Å EMDB-47936: mTORC1-Rag-Ragulator-4EBP1 complex on membrane with C2 symmetry 手法: EM (単粒子) / 解像度: 3.23 Å EMDB-47937: Focused refinement of the mTORC1-Rag-Ragulator-4EBP1 on membrane with mTOR-mLST8-Rheb mask 手法: EM (単粒子) / 解像度: 3.09 Å EMDB-47938: Focused refinement of the mTORC1-Rag-Ragulator-4EBP1 on membrane with Raptor-Rag-Ragulator mask 手法: EM (単粒子) / 解像度: 2.98 Å 47939 9ed7 EMDB-47939, PDB-9ed7: Active state of mTOR on membrane 手法: EM (単粒子) / 解像度: 3.16 Å 47940 9ed8 EMDB-47940, PDB-9ed8: Intermediate state of mTOR on membrane 手法: EM (単粒子) / 解像度: 3.61 Å
化合物	ChemComp-GSP: 5'-GUANOSINE-DIPHOSPHATE-MONOTHIOPHOSPHATE ChemComp-MG: Unknown entry ChemComp-ANP: PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER / AMP-PNP, エネルギー貯蔵分子類似体YM ChemComp-IHP: INOSITOL HEXAKISPHOSPHATE ChemComp-GTP: GUANOSINE-5'-TRIPHOSPHATE / GTP, エネルギー貯蔵分子YM ChemComp-GDP: GUANOSINE-5'-DIPHOSPHATE / GDP, エネルギー貯蔵分子*YM
由来	homo sapiens (ヒト)
キーワード	SIGNALING PROTEIN / mTORC1 / 4EBP1 / cell growth / singaling protein / membrane