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データを開く
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基本情報
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タイトル | Composite cryo-EM map of the Raptor-TFEB-Rag-Ragulator complex | |||||||||
![]() | A composite map of the Raptor-TFEB-Rag-Ragulator complex | |||||||||
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![]() | mTORC1 / TFEB / Lysosome biogenesis / Autophagy / SIGNALING PROTEIN | |||||||||
機能・相同性 | ![]() 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 / protein localization to cell junction / positive regulation of pentose-phosphate shunt ...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 / protein localization to cell junction / positive regulation of pentose-phosphate shunt / antibacterial innate immune response / regulation of TORC1 signaling / TORC1 complex / protein localization to lysosome / TORC1 signaling / positive regulation of odontoblast differentiation / regulation of TOR signaling / endosome organization / cellular response to L-leucine / MTOR signalling / Amino acids regulate mTORC1 / fibroblast migration / lysosome localization / Energy dependent regulation of mTOR by LKB1-AMPK / protein serine/threonine kinase inhibitor activity / protein localization to membrane / kinase activator activity / positive regulation of osteoclast differentiation / cellular response to osmotic stress / enzyme-substrate adaptor activity / positive regulation of transcription by RNA polymerase III / azurophil granule membrane / endosomal transport / regulation of cell size / Macroautophagy / small GTPase-mediated signal transduction / lysosome organization / RHOJ GTPase cycle / protein kinase activator activity / RHOQ GTPase cycle / mTORC1-mediated signalling / cellular response to nutrient levels / social behavior / tertiary granule membrane / CDC42 GTPase cycle / RHOH GTPase cycle / humoral immune response / ficolin-1-rich granule membrane / HSF1-dependent transactivation / RHOG GTPase cycle / positive regulation of TOR signaling / regulation of receptor recycling / TOR signaling / RAC2 GTPase cycle / embryonic placenta development / RAC3 GTPase cycle / response to amino acid / positive regulation of G1/S transition of mitotic cell cycle / positive regulation of autophagy / specific granule membrane / positive regulation of lipid biosynthetic process / protein-membrane adaptor activity / 14-3-3 protein binding / positive regulation of TORC1 signaling / positive regulation of endothelial cell proliferation / tumor necrosis factor-mediated signaling pathway / RAC1 GTPase cycle / cellular response to amino acid starvation / positive regulation of glycolytic process / cellular response to starvation / negative regulation of autophagy / viral genome replication / RNA splicing / guanyl-nucleotide exchange factor activity / positive regulation of peptidyl-threonine phosphorylation / Regulation of PTEN gene transcription / regulation of autophagy / positive regulation of interleukin-8 production / cholesterol homeostasis / regulation of cell growth / cellular response to glucose stimulus / 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 / response to virus / MAP2K and MAPK activation / negative regulation of cysteine-type endopeptidase activity involved in apoptotic process / protein localization / small GTPase binding / autophagy / cytoplasmic stress granule / positive regulation of protein localization to nucleus / GDP binding / sequence-specific double-stranded DNA binding / late endosome / E3 ubiquitin ligases ubiquitinate target proteins / GTPase binding / positive regulation of peptidyl-serine phosphorylation / glucose homeostasis 類似検索 - 分子機能 | |||||||||
生物種 | ![]() | |||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 2.9 Å | |||||||||
![]() | Cui Z / Hurley J | |||||||||
資金援助 | ![]()
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![]() | ![]() タイトル: Structure of the lysosomal mTORC1-TFEB-Rag-Ragulator megacomplex. 著者: Zhicheng Cui / Gennaro Napolitano / Mariana E G de Araujo / Alessandra Esposito / Jlenia Monfregola / Lukas A Huber / Andrea Ballabio / James H Hurley / ![]() ![]() ![]() 要旨: The transcription factor TFEB is a master regulator of lysosomal biogenesis and autophagy. The phosphorylation of TFEB by the mechanistic target of rapamycin complex 1 (mTORC1) is unique in its ...The transcription factor TFEB is a master regulator of lysosomal biogenesis and autophagy. The phosphorylation of TFEB by the mechanistic target of rapamycin complex 1 (mTORC1) is unique in its mTORC1 substrate recruitment mechanism, which is strictly dependent on the amino acid-mediated activation of the RagC GTPase activating protein FLCN. TFEB lacks the TOR signalling motif responsible for the recruitment of other mTORC1 substrates. We used cryogenic-electron microscopy to determine the structure of TFEB as presented to mTORC1 for phosphorylation, which we refer to as the 'megacomplex'. Two full Rag-Ragulator complexes present each molecule of TFEB to the mTOR active site. One Rag-Ragulator complex is bound to Raptor in the canonical mode seen previously in the absence of TFEB. A second Rag-Ragulator complex (non-canonical) docks onto the first through a RagC GDP-dependent contact with the second Ragulator complex. The non-canonical Rag dimer binds the first helix of TFEB with a RagC-dependent aspartate clamp in the cleft between the Rag G domains. In cellulo mutation of the clamp drives TFEB constitutively into the nucleus while having no effect on mTORC1 localization. The remainder of the 108-amino acid TFEB docking domain winds around Raptor and then back to RagA. The double use of RagC GDP contacts in both Rag dimers explains the strong dependence of TFEB phosphorylation on FLCN and the RagC GDP state. | |||||||||
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構造の表示
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ダウンロードとリンク
-EMDBアーカイブ
マップデータ | ![]() | 115.6 MB | ![]() | |
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ヘッダ (付随情報) | ![]() ![]() | 23.5 KB 23.5 KB | 表示 表示 | ![]() |
画像 | ![]() | 63.8 KB | ||
Filedesc metadata | ![]() | 7.8 KB | ||
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-検証レポート
文書・要旨 | ![]() | 493.6 KB | 表示 | ![]() |
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文書・詳細版 | ![]() | 493.2 KB | 表示 | |
XML形式データ | ![]() | 6.8 KB | 表示 | |
CIF形式データ | ![]() | 7.8 KB | 表示 | |
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-関連構造データ
関連構造データ | ![]() 7ux2MC ![]() 7uxcC ![]() 7uxhC C: 同じ文献を引用 ( M: このマップから作成された原子モデル |
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類似構造データ | 類似検索 - 機能・相同性 ![]() |
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リンク
EMDBのページ | ![]() ![]() |
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「今月の分子」の関連する項目 |
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マップ
ファイル | ![]() | ||||||||||||||||||||
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注釈 | A composite map of the Raptor-TFEB-Rag-Ragulator complex | ||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 1.05 Å | ||||||||||||||||||||
密度 |
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対称性 | 空間群: 1 | ||||||||||||||||||||
詳細 | EMDB XML:
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-添付データ
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試料の構成要素
+全体 : The Raptor-TFEB-Rag-Ragulator complex
+超分子 #1: The Raptor-TFEB-Rag-Ragulator complex
+分子 #1: Regulatory-associated protein of mTOR
+分子 #2: Ras-related GTP-binding protein A
+分子 #3: Ras-related GTP-binding protein C
+分子 #4: Ragulator complex protein LAMTOR1
+分子 #5: Ragulator complex protein LAMTOR2
+分子 #6: Ragulator complex protein LAMTOR3
+分子 #7: Ragulator complex protein LAMTOR4
+分子 #8: Ragulator complex protein LAMTOR5
+分子 #9: Transcription factor EB
+分子 #10: GUANOSINE-5'-TRIPHOSPHATE
+分子 #11: MAGNESIUM ION
+分子 #12: GUANOSINE-5'-DIPHOSPHATE
-実験情報
-構造解析
手法 | クライオ電子顕微鏡法 |
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![]() | 単粒子再構成法 |
試料の集合状態 | particle |
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試料調製
緩衝液 | pH: 7.4 |
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グリッド | モデル: C-flat-2/1 / 材質: COPPER / メッシュ: 300 / 前処理 - タイプ: GLOW DISCHARGE |
凍結 | 凍結剤: ETHANE |
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電子顕微鏡法
顕微鏡 | FEI TITAN KRIOS |
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撮影 | フィルム・検出器のモデル: GATAN K3 BIOQUANTUM (6k x 4k) 平均電子線量: 50.0 e/Å2 |
電子線 | 加速電圧: 300 kV / 電子線源: ![]() |
電子光学系 | 照射モード: FLOOD BEAM / 撮影モード: BRIGHT FIELD / 最大 デフォーカス(公称値): 2.2 µm / 最小 デフォーカス(公称値): 0.8 µm |
実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |
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画像解析
初期モデル | モデルのタイプ: INSILICO MODEL / In silico モデル: ab-initio reconstruction by cryoSPARC |
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最終 再構成 | 解像度のタイプ: BY AUTHOR / 解像度: 2.9 Å / 解像度の算出法: FSC 0.143 CUT-OFF / ソフトウェア - 名称: cryoSPARC (ver. 3.2) / 使用した粒子像数: 377569 |
初期 角度割当 | タイプ: MAXIMUM LIKELIHOOD |
最終 角度割当 | タイプ: MAXIMUM LIKELIHOOD |
-原子モデル構築 1
精密化 | 空間: REAL / プロトコル: AB INITIO MODEL |
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得られたモデル | ![]() PDB-7ux2: |