Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	Structural basis for mTORC1 activation on the lysosomal membrane.
Journal, issue, pages	Nature, Vol. 647, Issue 8089, Page 536-543, Year 2025
Publish date	Sep 17, 2025
Authors	Zhicheng Cui / Alessandra Esposito / Gennaro Napolitano / Andrea Ballabio / James H Hurley /
PubMed Abstract	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.
External links	Nature / PubMed:40963021 / PubMed Central
Methods	EM (single particle)
Resolution	2.98 - 3.98 Å
Structure data	47932 9ed4 EMDB-47932, PDB-9ed4: A composite map of mTORC1-Rag-Ragultor-4EBP1 on membrane Method: EM (single particle) / Resolution: 3.23 Å 47933 9ed6 EMDB-47933, PDB-9ed6: CryoEM map of the mLST8-Rag-Ragultor subcomplex Method: EM (single particle) / Resolution: 3.98 Å EMDB-47934: mTORC1-Rag-Ragulator-4EBP1 on membrane with two extra Rag-Ragulator Method: EM (single particle) / Resolution: 3.81 Å EMDB-47935: mTORC1-Rag-Ragulator-4EBP1 on membrane with one extra Rag-Ragulator Method: EM (single particle) / Resolution: 3.47 Å EMDB-47936: mTORC1-Rag-Ragulator-4EBP1 complex on membrane with C2 symmetry Method: EM (single particle) / Resolution: 3.23 Å EMDB-47937: Focused refinement of the mTORC1-Rag-Ragulator-4EBP1 on membrane with mTOR-mLST8-Rheb mask Method: EM (single particle) / Resolution: 3.09 Å EMDB-47938: Focused refinement of the mTORC1-Rag-Ragulator-4EBP1 on membrane with Raptor-Rag-Ragulator mask Method: EM (single particle) / Resolution: 2.98 Å 47939 9ed7 EMDB-47939, PDB-9ed7: Active state of mTOR on membrane Method: EM (single particle) / Resolution: 3.16 Å 47940 9ed8 EMDB-47940, PDB-9ed8: Intermediate state of mTOR on membrane Method: EM (single particle) / Resolution: 3.61 Å
Chemicals	ChemComp-GSP: 5'-GUANOSINE-DIPHOSPHATE-MONOTHIOPHOSPHATE ChemComp-MG: Unknown entry ChemComp-ANP: PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER / AMP-PNP, energy-carrying molecule analogueYM ChemComp-IHP: INOSITOL HEXAKISPHOSPHATE ChemComp-GTP: GUANOSINE-5'-TRIPHOSPHATE / GTP, energy-carrying moleculeYM ChemComp-GDP: GUANOSINE-5'-DIPHOSPHATE / GDP, energy-carrying molecule*YM
Source	homo sapiens (human)
Keywords	SIGNALING PROTEIN / mTORC1 / 4EBP1 / cell growth / singaling protein / membrane