signaling complex / GTPase / lysosome / 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 / Gtr1-Gtr2 GTPase complex / regulation of cholesterol efflux / FNIP-folliculin RagC/D GAP / Ragulator complex / protein localization to cell junction / positive regulation of pentose-phosphate shunt / regulation of TORC1 signaling ...regulation of cholesterol import / positive regulation of protein localization to lysosome / regulation of cell-substrate junction organization / Gtr1-Gtr2 GTPase complex / regulation of cholesterol efflux / FNIP-folliculin RagC/D GAP / Ragulator complex / protein localization to cell junction / positive regulation of pentose-phosphate shunt / regulation of TORC1 signaling / protein localization to lysosome / TORC1 complex / positive regulation of odontoblast differentiation / regulation of TOR signaling / Amino acids regulate mTORC1 / fibroblast migration / cellular response to L-leucine / MTOR signalling / lysosome localization / endosome organization / Energy dependent regulation of mTOR by LKB1-AMPK / TORC1 signaling / serine/threonine protein kinase complex / positive regulation of osteoclast differentiation / cellular response to osmotic stress / kinase activator activity / protein localization to membrane / protein serine/threonine kinase inhibitor activity / endosomal transport / azurophil granule membrane / positive regulation of transcription by RNA polymerase III / lysosome organization / positive regulation of peptidyl-threonine phosphorylation / small GTPase-mediated signal transduction / regulation of cell size / Macroautophagy / RHOJ GTPase cycle / RHOQ GTPase cycle / social behavior / TOR signaling / mTORC1-mediated signalling / tertiary granule membrane / CDC42 GTPase cycle / RHOH GTPase cycle / protein kinase activator activity / ficolin-1-rich granule membrane / RHOG GTPase cycle / regulation of receptor recycling / positive regulation of TOR signaling / response to amino acid / RAC2 GTPase cycle / HSF1-dependent transactivation / RAC3 GTPase cycle / positive regulation of G1/S transition of mitotic cell cycle / enzyme-substrate adaptor activity / cellular response to nutrient levels / positive regulation of lipid biosynthetic process / specific granule membrane / protein-membrane adaptor activity / positive regulation of peptidyl-serine phosphorylation / tumor necrosis factor-mediated signaling pathway / positive regulation of endothelial cell proliferation / 14-3-3 protein binding / RAC1 GTPase cycle / positive regulation of TORC1 signaling / negative regulation of autophagy / cellular response to amino acid starvation / RNA splicing / viral genome replication / cholesterol homeostasis / guanyl-nucleotide exchange factor activity / positive regulation of glycolytic process / cellular response to starvation / Regulation of PTEN gene transcription / positive regulation of interleukin-8 production / TP53 Regulates Metabolic Genes / phosphoprotein binding / cellular response to amino acid stimulus / regulation of cell growth / cellular response to glucose stimulus / MAP2K and MAPK activation / response to virus / small GTPase binding / positive regulation of protein localization to nucleus / cytoplasmic stress granule / GDP binding / late endosome membrane / late endosome / intracellular protein localization / glucose homeostasis / E3 ubiquitin ligases ubiquitinate target proteins / GTPase binding / positive regulation of cell growth / protein-macromolecule adaptor activity / 加水分解酵素; 酸無水物に作用; GTPに作用・細胞または細胞小器官の運動に関与 / cellular response to hypoxia / molecular adaptor activity / positive regulation of canonical NF-kappaB signal transduction / lysosome / positive regulation of MAPK cascade 類似検索 - 分子機能
LAMTOR1/MEH1 / Late endosomal/lysosomal adaptor and MAPK and MTOR activator / Late endosomal/lysosomal adaptor and MAPK and MTOR activator / Ragulator complex protein LAMTOR4 / Ragulator complex protein LAMTOR3 / Ragulator complex protein LAMTOR5 / RagA/B / 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 / Ragulator complex protein LAMTOR4 / Ragulator complex protein LAMTOR3 / Ragulator complex protein LAMTOR5 / RagA/B / Mitogen-activated protein kinase kinase 1 interacting / Ragulator complex protein LAMTOR5 / Mitogen-activated protein kinase kinase 1 interacting / Gtr1/RagA G protein / RagC/D / Gtr1/RagA G protein conserved region / Ragulator complex protein LAMTOR2-like / Raptor, N-terminal CASPase-like domain / Raptor N-terminal CASPase like domain / Raptor N-terminal CASPase like domain / Regulatory associated protein of TOR / Roadblock/LAMTOR2 domain / Roadblock/LC7 domain / Roadblock/LC7 domain / HEAT repeat / HEAT repeat / Armadillo-like helical / Armadillo-type fold / WD domain, G-beta repeat / Trp-Asp (WD) repeats circular profile. / WD40 repeats / WD40 repeat / WD40-repeat-containing domain superfamily / WD40/YVTN repeat-like-containing domain superfamily / P-loop containing nucleoside triphosphate hydrolase 類似検索 - ドメイン・相同性
Ragulator complex protein LAMTOR5 / Ragulator complex protein LAMTOR4 / Ragulator complex protein LAMTOR1 / Ras-related GTP-binding protein A / Regulatory-associated protein of mTOR / 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)
R01 CA103866
米国
National Institutes of Health/National Cancer Institute (NIH/NCI)
R01 CA129105
米国
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
R37 AI47389
米国
Department of Defense (DOD, United States)
W81XWH-07-0448
米国
Lustgarten Foundation
米国
Tuberous Sclerosis Association
英国
Howard Hughes Medical Institute (HHMI)
米国
American Cancer Society
米国
引用
ジャーナル: Science / 年: 2019 タイトル: Structural basis for the docking of mTORC1 on the lysosomal surface. 著者: Kacper B Rogala / Xin Gu / Jibril F Kedir / Monther Abu-Remaileh / Laura F Bianchi / Alexia M S Bottino / Rikke Dueholm / Anna Niehaus / Daan Overwijn / Ange-Célia Priso Fils / Sherry X Zhou ...著者: Kacper B Rogala / Xin Gu / Jibril F Kedir / Monther Abu-Remaileh / Laura F Bianchi / Alexia M S Bottino / Rikke Dueholm / Anna Niehaus / Daan Overwijn / Ange-Célia Priso Fils / Sherry X Zhou / Daniel Leary / Nouf N Laqtom / Edward J Brignole / David M Sabatini / 要旨: The mTORC1 (mechanistic target of rapamycin complex 1) protein kinase regulates growth in response to nutrients and growth factors. Nutrients promote its translocation to the lysosomal surface, where ...The mTORC1 (mechanistic target of rapamycin complex 1) protein kinase regulates growth in response to nutrients and growth factors. Nutrients promote its translocation to the lysosomal surface, where its Raptor subunit interacts with the Rag guanosine triphosphatase (GTPase)-Ragulator complex. Nutrients switch the heterodimeric Rag GTPases among four different nucleotide-binding states, only one of which (RagA/B•GTP-RagC/D•GDP) permits mTORC1 association. We used cryo-electron microscopy to determine the structure of the supercomplex of Raptor with Rag-Ragulator at a resolution of 3.2 angstroms. Our findings indicate that the Raptor α-solenoid directly detects the nucleotide state of RagA while the Raptor "claw" threads between the GTPase domains to detect that of RagC. Mutations that disrupted Rag-Raptor binding inhibited mTORC1 lysosomal localization and signaling. By comparison with a structure of mTORC1 bound to its activator Rheb, we developed a model of active mTORC1 docked on the lysosome.