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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 | cryo-EM structure of the mTORC1-TFEB-Rag-Ragulator complex with symmetry expansion | |||||||||
マップデータ | ||||||||||
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 / 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 / regulation of cholesterol efflux / Gtr1-Gtr2 GTPase complex / 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 / antibacterial innate immune response / TORC2 signaling / TORC2 complex / regulation of membrane permeability / regulation of TORC1 signaling / cellular response to leucine starvation / negative regulation of lysosome organization / heart valve morphogenesis / TFIIIC-class transcription factor complex binding / TORC1 complex / voluntary musculoskeletal movement / positive regulation of transcription of nucleolar large rRNA by RNA polymerase I / protein localization to lysosome / positive regulation of odontoblast differentiation / calcineurin-NFAT signaling cascade / RNA polymerase III type 3 promoter sequence-specific DNA binding / positive regulation of keratinocyte migration / regulation of osteoclast differentiation / regulation of lysosome organization / regulation of TOR signaling / MTOR signalling / fibroblast migration / cellular response to L-leucine / energy reserve metabolic process / lysosome localization / regulation of autophagosome assembly / Energy dependent regulation of mTOR by LKB1-AMPK / cellular response to nutrient / endosome organization / Amino acids regulate mTORC1 / TORC1 signaling / serine/threonine protein kinase complex / ruffle organization / cellular response to methionine / positive regulation of osteoclast differentiation / negative regulation of cell size / positive regulation of ubiquitin-dependent protein catabolic process / kinase activator activity / cellular response to osmotic stress / negative regulation of protein localization to nucleus / anoikis / protein localization to membrane / inositol hexakisphosphate binding / cardiac muscle cell development / negative regulation of calcineurin-NFAT signaling cascade / regulation of myelination / endosomal transport / positive regulation of transcription by RNA polymerase III / lysosome organization / azurophil granule membrane / small GTPase-mediated signal transduction / negative regulation of macroautophagy / Macroautophagy / positive regulation of myotube differentiation / regulation of cell size / RHOJ GTPase cycle / Constitutive Signaling by AKT1 E17K in Cancer / RHOQ GTPase cycle / positive regulation of actin filament polymerization / germ cell development / TOR signaling / behavioral response to pain / humoral immune response / oligodendrocyte differentiation / mTORC1-mediated signalling / positive regulation of oligodendrocyte differentiation / CDC42 GTPase cycle / tertiary granule membrane / positive regulation of translational initiation / RHOH GTPase cycle / ficolin-1-rich granule membrane / RHOG GTPase cycle / regulation of receptor recycling / social behavior / protein serine/threonine kinase inhibitor activity / CD28 dependent PI3K/Akt signaling / RAC2 GTPase cycle / HSF1-dependent transactivation / RAC3 GTPase cycle / positive regulation of TOR signaling / regulation of macroautophagy / protein kinase activator activity / enzyme-substrate adaptor activity / positive regulation of G1/S transition of mitotic cell cycle / embryonic placenta development 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_26857.map.gz | 43.3 MB | EMDBマップデータ形式 | |
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| ヘッダ (付随情報) | emd-26857-v30.xml emd-26857.xml | 31.2 KB 31.2 KB | 表示 表示 | EMDBヘッダ |
| FSC (解像度算出) | emd_26857_fsc.xml | 19.4 KB | 表示 | FSCデータファイル |
| 画像 | emd_26857.png | 86.1 KB | ||
| Filedesc metadata | emd-26857.cif.gz | 9.9 KB | ||
| その他 | emd_26857_half_map_1.map.gz emd_26857_half_map_2.map.gz | 720.4 MB 720.4 MB | ||
| アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-26857 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-26857 | HTTPS FTP |
-検証レポート
| 文書・要旨 | emd_26857_validation.pdf.gz | 837.5 KB | 表示 | EMDB検証レポート |
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| 文書・詳細版 | emd_26857_full_validation.pdf.gz | 837.1 KB | 表示 | |
| XML形式データ | emd_26857_validation.xml.gz | 29.3 KB | 表示 | |
| CIF形式データ | emd_26857_validation.cif.gz | 38.9 KB | 表示 | |
| アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-26857 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-26857 | 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 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_26857.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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| 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 | ||||||||||||||||||||||||||||||||||||
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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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| 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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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 |
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
引用





























Z (Sec.)
Y (Row.)
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解析
FIELD EMISSION GUN

