- EMDB-21686: CryoEM structure of the SLC38A9-RagA-RagC-Ragulator complex in th... -
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基本情報
登録情報
データベース: EMDB / ID: EMD-21686
タイトル
CryoEM structure of the SLC38A9-RagA-RagC-Ragulator complex in the pre-GAP state
マップデータ
Ragulator-RagA-GDP-RagC-XTPgS-SLC38A9; density modified with Phenix ResolveCryoEM and Phenix Autoshparpen Map
試料
複合体: Complex of pentameric Ragulator, dimeric Rag GTPases and SLC38A9
複合体: pentameric Ragulator
タンパク質・ペプチド: x 5種
複合体: dimeric Rag GTPases
タンパク質・ペプチド: x 2種
複合体: SLC38A9
タンパク質・ペプチド: x 1種
リガンド: x 3種
キーワード
small GTPase / mTORC1 activation / amino acid signaling / lysosome / SIGNALING PROTEIN
機能・相同性
機能・相同性情報
asparagine transport / L-asparagine transmembrane transporter activity / sterol sensor activity / L-arginine transmembrane transporter activity / regulation of cholesterol import / L-arginine transmembrane transport / positive regulation of protein localization to lysosome / regulation of cell-substrate junction organization / Gtr1-Gtr2 GTPase complex / regulation of cholesterol efflux ...asparagine transport / L-asparagine transmembrane transporter activity / sterol sensor activity / L-arginine transmembrane transporter activity / regulation of cholesterol import / L-arginine transmembrane transport / positive regulation of protein localization to lysosome / regulation of cell-substrate junction organization / Gtr1-Gtr2 GTPase complex / regulation of cholesterol efflux / L-glutamine transmembrane transporter activity / FNIP-folliculin RagC/D GAP / Ragulator complex / glutamine transport / protein localization to cell junction / amino acid transmembrane transport / L-leucine transmembrane transporter activity / regulation of TORC1 signaling / L-amino acid transmembrane transporter activity / protein localization to lysosome / regulation of TOR signaling / fibroblast migration / MTOR signalling / Amino acids regulate mTORC1 / lysosome localization / endosome organization / Energy dependent regulation of mTOR by LKB1-AMPK / TORC1 signaling / amino acid transmembrane transporter activity / kinase activator activity / arginine binding / protein localization to membrane / azurophil granule membrane / endosomal transport / lysosome organization / cholesterol binding / small GTPase-mediated signal transduction / Macroautophagy / regulation of cell size / RHOJ GTPase cycle / RHOQ GTPase cycle / 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 / RAC2 GTPase cycle / RAC3 GTPase cycle / enzyme-substrate adaptor activity / response to amino acid / cellular response to nutrient levels / specific granule membrane / protein-membrane adaptor activity / RAC1 GTPase cycle / positive regulation of TORC1 signaling / negative regulation of autophagy / RNA splicing / cellular response to amino acid starvation / viral genome replication / guanyl-nucleotide exchange factor activity / cholesterol homeostasis / cellular response to starvation / Regulation of PTEN gene transcription / tumor necrosis factor-mediated signaling pathway / 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 / positive regulation of protein localization to nucleus / GDP binding / late endosome membrane / E3 ubiquitin ligases ubiquitinate target proteins / late endosome / intracellular protein localization / glucose homeostasis / GTPase binding / molecular 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 / endosome membrane / lysosome / positive regulation of canonical NF-kappaB signal transduction / positive regulation of MAPK cascade / intracellular signal transduction / membrane raft / protein heterodimerization activity / lysosomal membrane / focal adhesion / intracellular membrane-bounded organelle / GTPase activity / ubiquitin protein ligase binding / DNA-templated transcription / apoptotic process / Neutrophil degranulation / positive regulation of gene expression 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 / Amino acid transporter, transmembrane domain / Ragulator complex protein LAMTOR4 / Transmembrane amino acid transporter protein / Ragulator complex protein LAMTOR3 / Ragulator complex protein LAMTOR5 / RagA/B / 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 / Amino acid transporter, transmembrane domain / Ragulator complex protein LAMTOR4 / Transmembrane amino acid transporter protein / 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 / 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 / Neutral amino acid transporter 9 / 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 Institute of General Medical Sciences (NIH/NIGMS)
R01GM111730
米国
引用
ジャーナル: Nat Struct Mol Biol / 年: 2020 タイトル: Structural mechanism for amino acid-dependent Rag GTPase nucleotide state switching by SLC38A9. 著者: Simon A Fromm / Rosalie E Lawrence / James H Hurley / 要旨: The Rag GTPases (Rags) recruit mTORC1 to the lysosomal membrane in response to nutrients, where it is then activated in response to energy and growth factor availability. The lysosomal folliculin ...The Rag GTPases (Rags) recruit mTORC1 to the lysosomal membrane in response to nutrients, where it is then activated in response to energy and growth factor availability. The lysosomal folliculin (FLCN) complex (LFC) consists of the inactive Rag dimer, the pentameric scaffold Ragulator, and the FLCN:FNIP2 (FLCN-interacting protein 2) GTPase activating protein (GAP) complex, and prevents Rag dimer activation during amino acid starvation. How the LFC is disassembled upon amino acid refeeding is an outstanding question. Here we show that the cytoplasmic tail of the human lysosomal solute carrier family 38 member 9 (SLC38A9) destabilizes the LFC and thereby triggers GAP activity of FLCN:FNIP2 toward RagC. We present the cryo-EM structures of Rags in complex with their lysosomal anchor complex Ragulator and the cytoplasmic tail of SLC38A9 in the pre- and post-GTP hydrolysis state of RagC, which explain how SLC38A9 destabilizes the LFC and so promotes Rag dimer activation.