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基本情報
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タイトル | cryo-EM structure of the mTORC1-TFEB-Rag-Ragulator complex with symmetry expansion | |||||||||
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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 / FNIP-folliculin RagC/D GAP / Ragulator complex / protein localization to cell junction / RNA polymerase III type 2 promoter sequence-specific DNA binding / RNA polymerase III type 1 promoter sequence-specific DNA binding ...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 / FNIP-folliculin RagC/D GAP / Ragulator complex / protein localization to cell junction / 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 / TORC2 signaling / TORC2 complex / regulation of membrane permeability / regulation of TORC1 signaling / antibacterial innate immune response / cellular response to leucine starvation / negative regulation of lysosome organization / heart valve morphogenesis / TFIIIC-class transcription factor complex binding / TORC1 complex / protein localization to lysosome / voluntary musculoskeletal movement / positive regulation of transcription of nucleolar large rRNA by RNA polymerase I / calcineurin-NFAT signaling cascade / positive regulation of odontoblast differentiation / regulation of osteoclast differentiation / RNA polymerase III type 3 promoter sequence-specific DNA binding / positive regulation of keratinocyte migration / regulation of TOR signaling / regulation of lysosome organization / fibroblast migration / MTOR signalling / Amino acids regulate mTORC1 / cellular response to nutrient / lysosome localization / energy reserve metabolic process / cellular response to L-leucine / endosome organization / regulation of autophagosome assembly / Energy dependent regulation of mTOR by LKB1-AMPK / TORC1 signaling / ruffle organization / serine/threonine protein kinase complex / cellular response to methionine / negative regulation of cell size / positive regulation of osteoclast differentiation / positive regulation of ubiquitin-dependent protein catabolic process / inositol hexakisphosphate binding / cellular response to osmotic stress / kinase activator activity / anoikis / negative regulation of protein localization to nucleus / protein localization to membrane / cardiac muscle cell development / negative regulation of calcineurin-NFAT signaling cascade / regulation of myelination / azurophil granule membrane / positive regulation of transcription by RNA polymerase III / endosomal transport / lysosome organization / negative regulation of macroautophagy / small GTPase-mediated signal transduction / Macroautophagy / positive regulation of myotube differentiation / regulation of cell size / RHOJ GTPase cycle / positive regulation of actin filament polymerization / Constitutive Signaling by AKT1 E17K in Cancer / RHOQ GTPase cycle / germ cell development / TOR signaling / behavioral response to pain / mTORC1-mediated signalling / oligodendrocyte differentiation / humoral immune response / positive regulation of oligodendrocyte differentiation / tertiary granule membrane / CDC42 GTPase cycle / positive regulation of translational initiation / RHOH GTPase cycle / ficolin-1-rich granule membrane / protein kinase activator activity / RHOG GTPase cycle / social behavior / regulation of receptor recycling / protein serine/threonine kinase inhibitor activity / CD28 dependent PI3K/Akt signaling / positive regulation of TOR signaling / HSF1-dependent transactivation / RAC2 GTPase cycle / RAC3 GTPase cycle / regulation of macroautophagy / enzyme-substrate adaptor activity / positive regulation of G1/S transition of mitotic cell cycle / response to amino acid 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: 3.2 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. | |||||||||
履歴 |
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構造の表示
添付画像 |
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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 | ![]() | 43.3 MB | ![]() | |
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ヘッダ (付随情報) | ![]() ![]() | 31.2 KB 31.2 KB | 表示 表示 | ![]() |
FSC (解像度算出) | ![]() | 19.4 KB | 表示 | ![]() |
画像 | ![]() | 86.1 KB | ||
Filedesc metadata | ![]() | 9.9 KB | ||
その他 | ![]() ![]() | 720.4 MB 720.4 MB | ||
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-検証レポート
文書・要旨 | ![]() | 837.5 KB | 表示 | ![]() |
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文書・詳細版 | ![]() | 837.1 KB | 表示 | |
XML形式データ | ![]() | 29.3 KB | 表示 | |
CIF形式データ | ![]() | 38.9 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 | ![]() 7uxcMC ![]() 7ux2C ![]() 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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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
-ハーフマップ: #2
ファイル | emd_26857_half_map_1.map | ||||||||||||
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投影像・断面図 |
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密度ヒストグラム |
-ハーフマップ: #1
ファイル | emd_26857_half_map_2.map | ||||||||||||
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投影像・断面図 |
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密度ヒストグラム |
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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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![]() | 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: ![]() |
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 |