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データを開く
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基本情報
| 登録情報 | ![]() | |||||||||
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| タイトル | A composite cryo-EM map of the mTORC1-TFEB-Rag-Ragulator complex | |||||||||
マップデータ | A composite map of the symmetric mTORC1-Rag-Ragulator complex | |||||||||
試料 |
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キーワード | mTORC1 / TFEB / Lysosome biogenesis / Autophagy / SIGNALING PROTEIN | |||||||||
| 機能・相同性 | 機能・相同性情報regulation of cholesterol import / positive regulation of protein localization to lysosome / regulation of cell-substrate junction organization / regulation of cholesterol efflux / Gtr1-Gtr2 GTPase complex / FNIP-folliculin RagC/D GAP / Ragulator complex / protein localization to cell junction / positive regulation of SCF-dependent proteasomal ubiquitin-dependent catabolic process / RNA polymerase III type 2 promoter sequence-specific DNA binding ...regulation of cholesterol import / positive regulation of protein localization to lysosome / regulation of cell-substrate junction organization / regulation of cholesterol efflux / Gtr1-Gtr2 GTPase complex / FNIP-folliculin RagC/D GAP / Ragulator complex / protein localization to cell junction / positive regulation of SCF-dependent proteasomal ubiquitin-dependent catabolic process / RNA polymerase III type 2 promoter sequence-specific DNA binding / RNA polymerase III type 1 promoter sequence-specific DNA binding / positive regulation of cytoplasmic translational initiation / regulation of locomotor rhythm / T-helper 1 cell lineage commitment / positive regulation of pentose-phosphate shunt / positive regulation of wound healing, spreading of epidermal cells / regulation of TORC1 signaling / TORC2 complex / regulation of membrane permeability / cellular response to leucine starvation / antibacterial innate immune response / TFIIIC-class transcription factor complex binding / heart valve morphogenesis / negative regulation of lysosome organization / TORC1 complex / voluntary musculoskeletal movement / positive regulation of odontoblast differentiation / positive regulation of transcription of nucleolar large rRNA by RNA polymerase I / calcineurin-NFAT signaling cascade / RNA polymerase III type 3 promoter sequence-specific DNA binding / positive regulation of keratinocyte migration / protein localization to lysosome / regulation of osteoclast differentiation / fibroblast migration / lysosome localization / MTOR signalling / regulation of lysosome organization / energy reserve metabolic process / cellular response to L-leucine / regulation of TOR signaling / regulation of autophagosome assembly / endosome organization / Energy dependent regulation of mTOR by LKB1-AMPK / cellular response to nutrient / Amino acids regulate mTORC1 / cellular response to methionine / TORC2 signaling / positive regulation of osteoclast differentiation / negative regulation of cell size / cellular response to osmotic stress / anoikis / kinase activator activity / cell projection organization / inositol hexakisphosphate binding / Phosphorylated BMAL1:CLOCK (ARNTL:CLOCK) activates expression of core clock genes / protein localization to membrane / cardiac muscle cell development / negative regulation of calcineurin-NFAT signaling cascade / positive regulation of ubiquitin-dependent protein catabolic process / regulation of myelination / negative regulation of protein localization to nucleus / positive regulation of transcription by RNA polymerase III / endosomal transport / azurophil granule membrane / positive regulation of ruffle assembly / regulation of cell size / small GTPase-mediated signal transduction / lysosome organization / negative regulation of macroautophagy / positive regulation of myotube differentiation / Macroautophagy / RHOJ GTPase cycle / Constitutive Signaling by AKT1 E17K in Cancer / RHOQ GTPase cycle / germ cell development / positive regulation of actin filament polymerization / humoral immune response / oligodendrocyte differentiation / CDC42 GTPase cycle / TORC1 signaling / behavioral response to pain / tertiary granule membrane / positive regulation of oligodendrocyte differentiation / TOR signaling / RHOH GTPase cycle / RHOG GTPase cycle / mTORC1-mediated signalling / ficolin-1-rich granule membrane / regulation of receptor recycling / response to amino acid / positive regulation of translational initiation / CD28 dependent PI3K/Akt signaling / RAC2 GTPase cycle / RAC3 GTPase cycle / HSF1-dependent transactivation / regulation of macroautophagy / positive regulation of TOR signaling / protein kinase activator activity / protein serine/threonine kinase inhibitor activity / enzyme-substrate adaptor activity 類似検索 - 分子機能 | |||||||||
| 生物種 | Homo sapiens (ヒト) | |||||||||
| 手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 3.2 Å | |||||||||
データ登録者 | Cui Z / Hurley J | |||||||||
| 資金援助 | 米国, 1件
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引用 | ジャーナル: Nature / 年: 2023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. | |||||||||
| 履歴 |
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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 | emd_26861.map.gz | 700.5 MB | EMDBマップデータ形式 | |
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| ヘッダ (付随情報) | emd-26861-v30.xml emd-26861.xml | 27.7 KB 27.7 KB | 表示 表示 | EMDBヘッダ |
| 画像 | emd_26861.png | 92.2 KB | ||
| Filedesc metadata | emd-26861.cif.gz | 9.9 KB | ||
| アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-26861 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-26861 | HTTPS FTP |
-関連構造データ
| 関連構造データ | ![]() 7uxhMC ![]() 7ux2C ![]() 7uxcC 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 F&H 検索 |
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リンク
| EMDBのページ | EMDB (EBI/PDBe) / EMDataResource |
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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 | ダウンロード / ファイル: emd_26861.map.gz / 形式: CCP4 / 大きさ: 775.5 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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| 注釈 | A composite map of the symmetric mTORC1-Rag-Ragulator complex | ||||||||||||||||||||||||||||||||||||
| 投影像・断面図 | 画像のコントロール
画像は Spider により作成 | ||||||||||||||||||||||||||||||||||||
| 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 mTORC1-TFEB-Rag-Ragulator complex
+超分子 #1: The mTORC1-TFEB-Rag-Ragulator complex
+分子 #1: Serine/threonine-protein kinase mTOR
+分子 #2: Target of rapamycin complex subunit LST8
+分子 #3: Regulatory-associated protein of mTOR
+分子 #4: Ras-related GTP-binding protein A
+分子 #5: Ras-related GTP-binding protein C
+分子 #6: Ragulator complex protein LAMTOR1
+分子 #7: Ragulator complex protein LAMTOR2
+分子 #8: Ragulator complex protein LAMTOR3
+分子 #9: Ragulator complex protein LAMTOR4
+分子 #10: Ragulator complex protein LAMTOR5
+分子 #11: Transcription factor EB
+分子 #12: INOSITOL HEXAKISPHOSPHATE
+分子 #13: GUANOSINE-5'-TRIPHOSPHATE
+分子 #14: MAGNESIUM ION
+分子 #15: 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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解析 | 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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| 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: FIELD EMISSION GUN |
| 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: 3.2 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: 192332 |
| 初期 角度割当 | タイプ: MAXIMUM LIKELIHOOD |
| 最終 角度割当 | タイプ: MAXIMUM LIKELIHOOD |
ムービー
コントローラー
万見について




キーワード
Homo sapiens (ヒト)
データ登録者
米国, 1件
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FIELD EMISSION GUN
