GATOR1 complex / 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 / negative regulation of kinase activity / FNIP-folliculin RagC/D GAP / Ragulator complex / protein localization to cell junction ...GATOR1 complex / 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 / negative regulation of kinase activity / FNIP-folliculin RagC/D GAP / Ragulator complex / protein localization to cell junction / aorta morphogenesis / regulation of TORC1 signaling / protein localization to lysosome / regulation of TOR signaling / endosome organization / Amino acids regulate mTORC1 / fibroblast migration / MTOR signalling / lysosome localization / Energy dependent regulation of mTOR by LKB1-AMPK / TORC1 signaling / kinase activator activity / protein localization to membrane / cardiac muscle tissue development / vacuolar membrane / ventricular septum development / endosomal transport / azurophil granule membrane / lysosome organization / small GTPase-mediated signal transduction / Macroautophagy / regulation of cell size / RHOJ GTPase cycle / RHOQ GTPase cycle / roof of mouth development / mTORC1-mediated signalling / tertiary granule membrane / CDC42 GTPase cycle / RHOH GTPase cycle / ficolin-1-rich granule membrane / RHOG GTPase cycle / regulation of receptor recycling / positive regulation of TOR signaling / response to amino acid / RAC2 GTPase cycle / RAC3 GTPase cycle / enzyme-substrate adaptor activity / cellular response to nutrient levels / specific granule membrane / protein-membrane adaptor activity / tumor necrosis factor-mediated signaling pathway / positive regulation of autophagy / negative regulation of TORC1 signaling / RAC1 GTPase cycle / positive regulation of TORC1 signaling / negative regulation of autophagy / cellular response to amino acid starvation / GTPase activator activity / RNA splicing / viral genome replication / cholesterol homeostasis / guanyl-nucleotide exchange factor activity / 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 / MAP2K and MAPK activation / response to virus / small GTPase binding / positive regulation of protein localization to nucleus / GDP binding / late endosome membrane / intracellular protein localization / late endosome / glucose homeostasis / E3 ubiquitin ligases ubiquitinate target proteins / GTPase binding / 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 / molecular adaptor activity / positive regulation of canonical NF-kappaB signal transduction / lysosome / positive regulation of MAPK cascade / endosome membrane / intracellular signal transduction / membrane raft / protein heterodimerization activity / lysosomal membrane / focal adhesion / GTPase activity / intracellular membrane-bounded organelle / DNA-templated transcription / apoptotic process / ubiquitin protein ligase binding / Neutrophil degranulation / positive regulation of gene expression / protein-containing complex binding / negative regulation of apoptotic process 類似検索 - 分子機能
: / IML1 N-terminal double psi beta barrel domain / Nitrogen permease regulator 3 / Nitrogen permease regulator 2 / Vacuolar membrane-associated protein Iml1 / DEPDC5 protein, C-terminal / : / Nitrogen Permease regulator of amino acid transport activity 3 / Nitrogen permease regulator 2 / Vacuolar membrane-associated protein Iml1, N-terminal domain ...: / IML1 N-terminal double psi beta barrel domain / Nitrogen permease regulator 3 / Nitrogen permease regulator 2 / Vacuolar membrane-associated protein Iml1 / DEPDC5 protein, C-terminal / : / Nitrogen Permease regulator of amino acid transport activity 3 / Nitrogen permease regulator 2 / Vacuolar membrane-associated protein Iml1, N-terminal domain / DEPDC5 protein C-terminal region / GATOR1 complex protein NPRL3, C-terminal HTH / 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 / Roadblock/LAMTOR2 domain / Roadblock/LC7 domain / Roadblock/LC7 domain / Domain found in Dishevelled, Egl-10, and Pleckstrin (DEP) / DEP domain profile. / Domain found in Dishevelled, Egl-10, and Pleckstrin / DEP domain / Winged helix DNA-binding domain superfamily / Winged helix-like DNA-binding domain superfamily / P-loop containing nucleoside triphosphate hydrolase 類似検索 - ドメイン・相同性
Ragulator complex protein LAMTOR5 / GATOR1 complex protein DEPDC5 / Ragulator complex protein LAMTOR4 / GATOR1 complex protein NPRL3 / Ragulator complex protein LAMTOR1 / Ras-related GTP-binding protein A / GATOR1 complex protein NPRL2 / 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)
米国
引用
ジャーナル: Mol Cell / 年: 2022 タイトル: Cryo-EM structures of the human GATOR1-Rag-Ragulator complex reveal a spatial-constraint regulated GAP mechanism. 著者: Shawn B Egri / Christna Ouch / Hui-Ting Chou / Zhiheng Yu / Kangkang Song / Chen Xu / Kuang Shen / 要旨: mTORC1 controls cellular metabolic processes in response to nutrient availability. Amino acid signals are transmitted to mTORC1 through the Rag GTPases, which are localized on the lysosomal surface ...mTORC1 controls cellular metabolic processes in response to nutrient availability. Amino acid signals are transmitted to mTORC1 through the Rag GTPases, which are localized on the lysosomal surface by the Ragulator complex. The Rag GTPases receive amino acid signals from multiple upstream regulators. One negative regulator, GATOR1, is a GTPase activating protein (GAP) for RagA. GATOR1 binds to the Rag GTPases via two modes: an inhibitory mode and a GAP mode. How these two binding interactions coordinate to process amino acid signals is unknown. Here, we resolved three cryo-EM structural models of the GATOR1-Rag-Ragulator complex, with the Rag-Ragulator subcomplex occupying the inhibitory site, the GAP site, and both binding sites simultaneously. When the Rag GTPases bind to GATOR1 at the GAP site, both Rag subunits contact GATOR1 to coordinate their nucleotide loading states. These results reveal a potential GAP mechanism of GATOR1 during the mTORC1 inactivation process.