SIGNALING PROTEIN / mTORC1 amino-acid sensing lysosome growth control
機能・相同性
機能・相同性情報
GATOR1 complex / Gtr1-Gtr2 GTPase complex / FNIP-folliculin RagC/D GAP / aorta morphogenesis / regulation of TORC1 signaling / protein localization to lysosome / TORC1 signaling / regulation of TOR signaling / MTOR signalling / Amino acids regulate mTORC1 ...GATOR1 complex / Gtr1-Gtr2 GTPase complex / FNIP-folliculin RagC/D GAP / aorta morphogenesis / regulation of TORC1 signaling / protein localization to lysosome / TORC1 signaling / regulation of TOR signaling / MTOR signalling / Amino acids regulate mTORC1 / Energy dependent regulation of mTOR by LKB1-AMPK / protein localization to membrane / enzyme-substrate adaptor activity / cardiac muscle tissue development / negative regulation of TOR signaling / vacuolar membrane / ventricular septum development / negative regulation of kinase activity / Macroautophagy / small GTPase-mediated signal transduction / roof of mouth development / mTORC1-mediated signalling / cellular response to nutrient levels / positive regulation of TOR signaling / response to amino acid / positive regulation of autophagy / protein-membrane adaptor activity / negative regulation of TORC1 signaling / positive regulation of TORC1 signaling / tumor necrosis factor-mediated signaling pathway / cellular response to amino acid starvation / cellular response to starvation / negative regulation of autophagy / RNA splicing / GTPase activator activity / Regulation of PTEN gene transcription / TP53 Regulates Metabolic Genes / phosphoprotein binding / cellular response to amino acid stimulus / 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 / protein localization / small GTPase binding / GDP binding / E3 ubiquitin ligases ubiquitinate target proteins / GTPase binding / glucose homeostasis / molecular adaptor activity / lysosome / intracellular signal transduction / protein heterodimerization activity / lysosomal membrane / intracellular membrane-bounded organelle / GTPase activity / DNA-templated transcription / apoptotic process / ubiquitin protein ligase binding / protein-containing complex binding / GTP binding / perinuclear region of cytoplasm / magnesium ion binding / protein homodimerization activity / nucleoplasm / nucleus / cytoplasm / cytosol 類似検索 - 分子機能
Beta-Lactamase - #190 / : / 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 ...Beta-Lactamase - #190 / : / 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 / RagA/B / Gtr1/RagA G protein / RagC/D / Gtr1/RagA G protein conserved region / Domain found in Dishevelled, Egl-10, and Pleckstrin (DEP) / DEP domain profile. / Domain found in Dishevelled, Egl-10, and Pleckstrin / DEP domain / Beta-Lactamase / P-loop containing nucleotide triphosphate hydrolases / Winged helix DNA-binding domain superfamily / Winged helix-like DNA-binding domain superfamily / P-loop containing nucleoside triphosphate hydrolase / Rossmann fold / 2-Layer Sandwich / 3-Layer(aba) Sandwich / Alpha Beta 類似検索 - ドメイン・相同性
PHOSPHOAMINOPHOSPHONIC ACID-GUANYLATE ESTER / GATOR1 complex protein DEPDC5 / GATOR1 complex protein NPRL3 / Ras-related GTP-binding protein A / GATOR1 complex protein NPRL2 / Ras-related GTP-binding protein C 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-15-1-0230
米国
National Science Foundation (NSF, United States)
2016197106
米国
Howard Hughes Medical Institute (HHMI)
米国
Life Sciences Research Foundation
米国
引用
ジャーナル: Nature / 年: 2018 タイトル: Architecture of the human GATOR1 and GATOR1-Rag GTPases complexes. 著者: Kuang Shen / Rick K Huang / Edward J Brignole / Kendall J Condon / Max L Valenstein / Lynne Chantranupong / Aimaiti Bomaliyamu / Abigail Choe / Chuan Hong / Zhiheng Yu / David M Sabatini / 要旨: Nutrients, such as amino acids and glucose, signal through the Rag GTPases to activate mTORC1. The GATOR1 protein complex-comprising DEPDC5, NPRL2 and NPRL3-regulates the Rag GTPases as a GTPase- ...Nutrients, such as amino acids and glucose, signal through the Rag GTPases to activate mTORC1. The GATOR1 protein complex-comprising DEPDC5, NPRL2 and NPRL3-regulates the Rag GTPases as a GTPase-activating protein (GAP) for RAGA; loss of GATOR1 desensitizes mTORC1 signalling to nutrient starvation. GATOR1 components have no sequence homology to other proteins, so the function of GATOR1 at the molecular level is currently unknown. Here we used cryo-electron microscopy to solve structures of GATOR1 and GATOR1-Rag GTPases complexes. GATOR1 adopts an extended architecture with a cavity in the middle; NPRL2 links DEPDC5 and NPRL3, and DEPDC5 contacts the Rag GTPase heterodimer. Biochemical analyses reveal that our GATOR1-Rag GTPases structure is inhibitory, and that at least two binding modes must exist between the Rag GTPases and GATOR1. Direct interaction of DEPDC5 with RAGA inhibits GATOR1-mediated stimulation of GTP hydrolysis by RAGA, whereas weaker interactions between the NPRL2-NPRL3 heterodimer and RAGA execute GAP activity. These data reveal the structure of a component of the nutrient-sensing mTORC1 pathway and a non-canonical interaction between a GAP and its substrate GTPase.
N: GATOR complex protein NPRL2 M: GATOR complex protein NPRL3 D: GATOR complex protein DEPDC5 A: Ras-related GTP-binding protein A C: Ras-related GTP-binding protein C ヘテロ分子
GATORcomplexproteinNPRL2 / Gene 21 protein / G21 protein / Nitrogen permease regulator 2-like protein / NPR2-like protein / ...Gene 21 protein / G21 protein / Nitrogen permease regulator 2-like protein / NPR2-like protein / Tumor suppressor candidate 4