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 / positive regulation of RNA polymerase II regulatory region sequence-specific DNA binding / FNIP-folliculin RagC/D GAP / Ragulator complex / aorta morphogenesis ...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 / positive regulation of RNA polymerase II regulatory region sequence-specific DNA binding / FNIP-folliculin RagC/D GAP / Ragulator complex / aorta morphogenesis / protein localization to cell junction / regulation of TORC1 signaling / protein localization to lysosome / regulation of TOR signaling / TORC1 signaling / endosome organization / fibroblast migration / MTOR signalling / Amino acids regulate mTORC1 / lysosome localization / Energy dependent regulation of mTOR by LKB1-AMPK / kinase activator activity / protein localization to membrane / cardiac muscle tissue development / enzyme-substrate adaptor activity / vacuolar membrane / ventricular septum development / azurophil granule membrane / endosomal transport / regulation of cell size / negative regulation of kinase activity / small GTPase-mediated signal transduction / Macroautophagy / lysosome organization / roof of mouth development / RHOJ GTPase cycle / RHOQ GTPase cycle / mTORC1-mediated signalling / tertiary granule membrane / CDC42 GTPase cycle / ficolin-1-rich granule membrane / RHOH GTPase cycle / RHOG GTPase cycle / regulation of receptor recycling / positive regulation of TOR signaling / RAC2 GTPase cycle / RAC3 GTPase cycle / response to amino acid / cellular response to nutrient levels / positive regulation of autophagy / specific granule membrane / protein-membrane adaptor activity / negative regulation of TORC1 signaling / Regulation of PTEN gene transcription / tumor necrosis factor-mediated signaling pathway / RAC1 GTPase cycle / positive regulation of TORC1 signaling / cellular response to starvation / cellular response to amino acid starvation / GTPase activator activity / viral genome replication / negative regulation of autophagy / cellular response to amino acid stimulus / RNA splicing / negative regulation of cysteine-type endopeptidase activity involved in apoptotic process / guanyl-nucleotide exchange factor activity / cholesterol homeostasis / positive regulation of interleukin-8 production / regulation of cell growth / TP53 Regulates Metabolic Genes / phosphoprotein 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 / response to virus / MAP2K and MAPK activation / small GTPase binding / positive regulation of protein localization to nucleus / GDP binding / protein localization / glucose homeostasis / late endosome / E3 ubiquitin ligases ubiquitinate target proteins / GTPase binding / late endosome membrane / positive regulation of NF-kappaB transcription factor activity / positive regulation of canonical NF-kappaB signal transduction / positive regulation of MAPK cascade / molecular adaptor activity / endosome membrane / lysosome / intracellular signal transduction / membrane raft / protein heterodimerization activity / lysosomal membrane / intracellular membrane-bounded organelle / focal adhesion / GTPase activity / DNA-templated transcription / ubiquitin protein ligase binding / Neutrophil degranulation / positive regulation of gene expression 類似検索 - 分子機能
DEPDC5 protein, C-terminal / DEPDC5 protein C-terminal region / Nitrogen permease regulator 3 / Nitrogen permease regulator 2 / Vacuolar membrane-associated protein Iml1 / : / Nitrogen Permease regulator of amino acid transport activity 3 / Nitrogen permease regulator 2 / Vacuolar membrane-associated protein Iml1, N-terminal domain / LAMTOR1/MEH1 ...DEPDC5 protein, C-terminal / DEPDC5 protein C-terminal region / Nitrogen permease regulator 3 / Nitrogen permease regulator 2 / Vacuolar membrane-associated protein Iml1 / : / Nitrogen Permease regulator of amino acid transport activity 3 / Nitrogen permease regulator 2 / Vacuolar membrane-associated protein Iml1, N-terminal domain / 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.