- EMDB-47932: A composite map of mTORC1-Rag-Ragultor-4EBP1 on membrane -
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基本情報
登録情報
データベース: EMDB / ID: EMD-47932
タイトル
A composite map of mTORC1-Rag-Ragultor-4EBP1 on membrane
マップデータ
A composite map of mLST8-mTOR-Rheb and Raptor-Rag-Ragulator subcomplexes
試料
複合体: The mTORC1-Rag-Ragulator-4EBP1 complex on membrane
タンパク質・ペプチド: x 12種
リガンド: x 6種
キーワード
mTORC1 / 4EBP1 / cell growth / singaling protein / membrane / SIGNALING PROTEIN
機能・相同性
機能・相同性情報
regulation of cholesterol import / positive regulation of protein localization to lysosome / regulation of cell-substrate junction organization / regulation of cholesterol efflux / Gtr1-Gtr2 GTPase complex / FNIP-folliculin RagC/D GAP / Ragulator complex / regulation of type B pancreatic cell development / protein localization to cell junction / Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S ...regulation of cholesterol import / positive regulation of protein localization to lysosome / regulation of cell-substrate junction organization / regulation of cholesterol efflux / Gtr1-Gtr2 GTPase complex / FNIP-folliculin RagC/D GAP / Ragulator complex / regulation of type B pancreatic cell development / protein localization to cell junction / Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S / positive regulation of SCF-dependent proteasomal ubiquitin-dependent catabolic process / RNA polymerase III type 2 promoter sequence-specific DNA binding / eukaryotic initiation factor 4E binding / RNA polymerase III type 1 promoter sequence-specific DNA binding / positive regulation of cytoplasmic translational initiation / regulation of locomotor rhythm / T-helper 1 cell lineage commitment / positive regulation of pentose-phosphate shunt / positive regulation of wound healing, spreading of epidermal cells / regulation of TORC1 signaling / TORC2 complex / regulation of membrane permeability / cellular response to leucine starvation / TFIIIC-class transcription factor complex binding / heart valve morphogenesis / negative regulation of lysosome organization / TORC1 complex / voluntary musculoskeletal movement / positive regulation of odontoblast differentiation / positive regulation of transcription of nucleolar large rRNA by RNA polymerase I / calcineurin-NFAT signaling cascade / RNA polymerase III type 3 promoter sequence-specific DNA binding / positive regulation of keratinocyte migration / protein localization to lysosome / regulation of osteoclast differentiation / fibroblast migration / lysosome localization / MTOR signalling / regulation of lysosome organization / energy reserve metabolic process / cellular response to L-leucine / regulation of TOR signaling / regulation of autophagosome assembly / endosome organization / Energy dependent regulation of mTOR by LKB1-AMPK / cellular response to nutrient / Amino acids regulate mTORC1 / cellular response to methionine / TORC2 signaling / positive regulation of osteoclast differentiation / negative regulation of cell size / cellular response to osmotic stress / anoikis / kinase activator activity / cell projection organization / inositol hexakisphosphate binding / protein localization to membrane / negative regulation of cold-induced thermogenesis / cardiac muscle cell development / negative regulation of calcineurin-NFAT signaling cascade / positive regulation of ubiquitin-dependent protein catabolic process / regulation of myelination / negative regulation of protein localization to nucleus / positive regulation of transcription by RNA polymerase III / endosomal transport / azurophil granule membrane / positive regulation of ruffle assembly / regulation of cell size / small GTPase-mediated signal transduction / lysosome organization / negative regulation of macroautophagy / positive regulation of myotube differentiation / Macroautophagy / RHOJ GTPase cycle / Constitutive Signaling by AKT1 E17K in Cancer / RHOQ GTPase cycle / germ cell development / positive regulation of actin filament polymerization / oligodendrocyte differentiation / CDC42 GTPase cycle / TORC1 signaling / behavioral response to pain / tertiary granule membrane / positive regulation of oligodendrocyte differentiation / TOR signaling / RHOH GTPase cycle / RHOG GTPase cycle / mTORC1-mediated signalling / ficolin-1-rich granule membrane / regulation of receptor recycling / response to amino acid / positive regulation of translational initiation / CD28 dependent PI3K/Akt signaling / RAC2 GTPase cycle / RAC3 GTPase cycle / HSF1-dependent transactivation / regulation of macroautophagy / positive regulation of TOR signaling / protein kinase activator activity / protein serine/threonine kinase inhibitor activity 類似検索 - 分子機能
Eukaryotic translation initiation factor 4E binding / Eukaryotic translation initiation factor 4E binding protein (EIF4EBP) / Ragulator complex protein LAMTOR4 / Ragulator complex protein LAMTOR3 / Ragulator complex protein LAMTOR5 / Mitogen-activated protein kinase kinase 1 interacting / Ragulator complex protein LAMTOR5 / Mitogen-activated protein kinase kinase 1 interacting / LAMTOR1/MEH1 / Late endosomal/lysosomal adaptor and MAPK and MTOR activator ...Eukaryotic translation initiation factor 4E binding / Eukaryotic translation initiation factor 4E binding protein (EIF4EBP) / Ragulator complex protein LAMTOR4 / Ragulator complex protein LAMTOR3 / Ragulator complex protein LAMTOR5 / Mitogen-activated protein kinase kinase 1 interacting / Ragulator complex protein LAMTOR5 / Mitogen-activated protein kinase kinase 1 interacting / LAMTOR1/MEH1 / Late endosomal/lysosomal adaptor and MAPK and MTOR activator / Late endosomal/lysosomal adaptor and MAPK and MTOR activator / RagA/B / RagC/D / Gtr1/RagA G protein / Gtr1/RagA G protein conserved region / Raptor, N-terminal CASPase-like domain / Ragulator complex protein LAMTOR2-like / Raptor N-terminal CASPase like domain / Raptor N-terminal CASPase like domain / Regulatory associated protein of TOR / Target of rapamycin complex subunit LST8 / Roadblock/LAMTOR2 domain / Domain of unknown function DUF3385, target of rapamycin protein / Roadblock/LC7 domain / Serine/threonine-protein kinase mTOR domain / Roadblock/LC7 domain / Domain of unknown function / FKBP12-rapamycin binding domain / Serine/threonine-protein kinase TOR / FKBP12-rapamycin binding domain superfamily / FKBP12-rapamycin binding domain / HEAT repeat / HEAT repeat / Rapamycin binding domain / : / Serine/threonine-protein kinase ATR-like, HEAT repeats / : / FATC domain / PIK-related kinase, FAT / FAT domain / FATC / FATC domain / PIK-related kinase / FAT domain profile. / FATC domain profile. / Quinoprotein alcohol dehydrogenase-like superfamily / Phosphatidylinositol 3- and 4-kinases signature 1. / Phosphatidylinositol 3/4-kinase, conserved site / Phosphatidylinositol 3- and 4-kinases signature 2. / Phosphatidylinositol 3-/4-kinase, catalytic domain superfamily / Phosphoinositide 3-kinase, catalytic domain / Small GTPase, Ras-type / Phosphatidylinositol 3- and 4-kinase / Phosphatidylinositol 3- and 4-kinases catalytic domain profile. / Phosphatidylinositol 3-/4-kinase, catalytic domain / Small GTPase Ras domain profile. / Rho (Ras homology) subfamily of Ras-like small GTPases / Ras subfamily of RAS small GTPases / Small GTPase / Ras family / Rab subfamily of small GTPases / Armadillo-like helical / Small GTP-binding protein domain / Tetratricopeptide-like helical domain superfamily / WD domain, G-beta repeat / Armadillo-type fold / G-protein beta WD-40 repeat / WD40 repeat, conserved site / Trp-Asp (WD) repeats signature. / Trp-Asp (WD) repeats profile. / Trp-Asp (WD) repeats circular profile. / WD40 repeats / WD40 repeat / WD40-repeat-containing domain superfamily / WD40/YVTN repeat-like-containing domain superfamily / Protein kinase-like domain superfamily / P-loop containing nucleoside triphosphate hydrolase 類似検索 - ドメイン・相同性
Ragulator complex protein LAMTOR5 / Serine/threonine-protein kinase mTOR / Ragulator complex protein LAMTOR4 / Eukaryotic translation initiation factor 4E-binding protein 1 / GTP-binding protein Rheb / Ragulator complex protein LAMTOR1 / Ras-related GTP-binding protein A / Regulatory-associated protein of mTOR / Target of rapamycin complex subunit LST8 / Ras-related GTP-binding protein C ...Ragulator complex protein LAMTOR5 / Serine/threonine-protein kinase mTOR / Ragulator complex protein LAMTOR4 / Eukaryotic translation initiation factor 4E-binding protein 1 / GTP-binding protein Rheb / Ragulator complex protein LAMTOR1 / Ras-related GTP-binding protein A / Regulatory-associated protein of mTOR / Target of rapamycin complex subunit LST8 / Ras-related GTP-binding protein C / Ragulator complex protein LAMTOR3 / Ragulator complex protein LAMTOR2 類似検索 - 構成要素
National Institutes of Health/National Cancer Institute (NIH/NCI)
CA285366
米国
引用
ジャーナル: Nature / 年: 2025 タイトル: Structural basis for mTORC1 activation on the lysosomal membrane. 著者: Zhicheng Cui / Alessandra Esposito / Gennaro Napolitano / Andrea Ballabio / James H Hurley / 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.