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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 | CryoEM map of the mLST8-Rag-Ragultor subcomplex | |||||||||
マップデータ | ||||||||||
試料 |
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キーワード | mTORC1 / cell growth / singaling protein / membrane / 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 pentose-phosphate shunt / TORC2 complex ...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 pentose-phosphate shunt / TORC2 complex / regulation of TORC1 signaling / TORC1 complex / protein localization to lysosome / MTOR signalling / fibroblast migration / lysosome localization / Energy dependent regulation of mTOR by LKB1-AMPK / regulation of TOR signaling / endosome organization / Amino acids regulate mTORC1 / TORC2 signaling / cellular response to osmotic stress / kinase activator activity / protein localization to membrane / endosomal transport / azurophil granule membrane / regulation of cell size / small GTPase-mediated signal transduction / lysosome organization / Macroautophagy / RHOJ GTPase cycle / Constitutive Signaling by AKT1 E17K in Cancer / RHOQ GTPase cycle / positive regulation of actin filament polymerization / TORC1 signaling / CDC42 GTPase cycle / TOR signaling / tertiary granule membrane / RHOH GTPase cycle / mTORC1-mediated signalling / response to amino acid / RHOG GTPase cycle / regulation of receptor recycling / ficolin-1-rich granule membrane / CD28 dependent PI3K/Akt signaling / RAC2 GTPase cycle / HSF1-dependent transactivation / RAC3 GTPase cycle / positive regulation of TOR signaling / enzyme-substrate adaptor activity / positive regulation of lipid biosynthetic process / specific granule membrane / protein-membrane adaptor activity / RAC1 GTPase cycle / cytoskeleton organization / positive regulation of TORC1 signaling / cellular response to nutrient levels / guanyl-nucleotide exchange factor activity / RNA splicing / viral genome replication / cellular response to amino acid starvation / positive regulation of glycolytic process / cholesterol homeostasis / cellular response to starvation / Regulation of PTEN gene transcription / tumor necrosis factor-mediated signaling pathway / negative regulation of autophagy / VEGFR2 mediated vascular permeability / positive regulation of interleukin-8 production / protein serine/threonine kinase activator activity / TP53 Regulates Metabolic Genes / regulation of actin cytoskeleton organization / cellular response to amino acid stimulus / regulation of cell growth / phosphoprotein binding / MAP2K and MAPK activation / positive regulation of protein localization to nucleus / response to virus / GDP binding / Regulation of TP53 Degradation / intracellular protein localization / late endosome / PIP3 activates AKT signaling / late endosome membrane / glucose homeostasis / E3 ubiquitin ligases ubiquitinate target proteins / positive regulation of cell growth / GTPase binding / High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells / cellular response to hypoxia / 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 / protein-macromolecule adaptor activity / positive regulation of canonical NF-kappaB signal transduction / positive regulation of MAPK cascade / lysosome / endosome membrane / intracellular signal transduction / membrane raft / protein heterodimerization 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: 3.98 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: 2025タイトル: Structural basis for mTORC1 activation on the lysosomal membrane. 著者: Zhicheng Cui / Alessandra Esposito / Gennaro Napolitano / Andrea Ballabio / James H Hurley / ![]() 要旨: The mechanistic target of rapamycin complex 1 (mTORC1) integrates growth factor (GF) and nutrient signals to stimulate anabolic processes connected to cell growth and inhibit catabolic processes such ...The mechanistic target of rapamycin complex 1 (mTORC1) integrates growth factor (GF) and nutrient signals to stimulate anabolic processes connected to cell growth and inhibit catabolic processes such as autophagy. GF signalling through the tuberous sclerosis complex regulates the lysosomally localized small GTPase RAS homologue enriched in brain (RHEB). Direct binding of RHEB-GTP to the mTOR kinase subunit of mTORC1 allosterically activates the kinase by inducing a large-scale conformational change. Here we reconstituted mTORC1 activation on membranes by RHEB, RAGs and Ragulator. Cryo-electron microscopy showed that RAPTOR and mTOR interact directly with the membrane. Full engagement of the membrane anchors is required for optimal alignment of the catalytic residues in the mTOR kinase active site. Converging signals from GFs and nutrients drive mTORC1 recruitment to and activation on lysosomal membrane in a four-step process, consisting of (1) RAG-Ragulator-driven recruitment to within ~100 Å of the lysosomal membrane; (2) RHEB-driven recruitment to within ~40 Å; (3) RAPTOR-membrane engagement and intermediate enzyme activation; and (4) mTOR-membrane engagement and full enzyme activation. RHEB and membrane engagement combined leads to full catalytic activation and structurally explains GF and nutrient signal integration at the lysosome. | |||||||||
| 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_47933.map.gz | 323.6 MB | EMDBマップデータ形式 | |
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| ヘッダ (付随情報) | emd-47933-v30.xml emd-47933.xml | 26.8 KB 26.8 KB | 表示 表示 | EMDBヘッダ |
| FSC (解像度算出) | emd_47933_fsc.xml | 14.9 KB | 表示 | FSCデータファイル |
| 画像 | emd_47933.png | 39 KB | ||
| Filedesc metadata | emd-47933.cif.gz | 7.4 KB | ||
| その他 | emd_47933_half_map_1.map.gz emd_47933_half_map_2.map.gz | 318.7 MB 318.7 MB | ||
| アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-47933 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-47933 | HTTPS FTP |
-関連構造データ
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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_47933.map.gz / 形式: CCP4 / 大きさ: 343 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: 1.04 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_47933_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_47933_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 : mLST8-Rag-Ragultor subcomplex
+超分子 #1: mLST8-Rag-Ragultor subcomplex
+分子 #1: Ras-related GTP-binding protein A
+分子 #2: Ragulator complex protein LAMTOR2
+分子 #3: Ragulator complex protein LAMTOR3
+分子 #4: Ragulator complex protein LAMTOR5
+分子 #5: Target of rapamycin complex subunit LST8
+分子 #6: Ras-related GTP-binding protein C
+分子 #7: Ragulator complex protein LAMTOR1
+分子 #8: Ragulator complex protein LAMTOR4
+分子 #9: GUANOSINE-5'-TRIPHOSPHATE
+分子 #10: MAGNESIUM ION
+分子 #11: 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 | TFS 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: 30.0 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): 2.0 µm / 最小 デフォーカス(公称値): 0.9 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.)
X (Col.)






































解析
FIELD EMISSION GUN

