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データを開く
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基本情報
登録情報 | データベース: EMDB / ID: EMD-0556 | |||||||||
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タイトル | Cryo-EM Map of the active Ragulator-RagA-RagC Complex | |||||||||
![]() | em-volume_P1 | |||||||||
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機能・相同性 | ![]() negative regulation of cell proliferation involved in kidney development / negative regulation of post-translational protein modification / cell proliferation involved in kidney development / 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 ...negative regulation of cell proliferation involved in kidney development / negative regulation of post-translational protein modification / cell proliferation involved in kidney development / 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 / negative regulation of brown fat cell differentiation / regulation of Ras protein signal transduction / protein localization to cell junction / regulation of TORC1 signaling / negative regulation of lysosome organization / regulation of pro-B cell differentiation / protein localization to lysosome / regulation of TOR signaling / TORC1 signaling / endosome organization / fibroblast migration / MTOR signalling / Amino acids regulate mTORC1 / lysosome localization / ATPase inhibitor activity / Energy dependent regulation of mTOR by LKB1-AMPK / kinase activator activity / protein localization to membrane / negative regulation of TOR signaling / enzyme inhibitor activity / enzyme-substrate adaptor activity / negative regulation of glycolytic process / cell-cell junction assembly / negative regulation of cold-induced thermogenesis / negative regulation of Rho protein signal transduction / azurophil granule membrane / endosomal transport / regulation of cell size / small GTPase-mediated signal transduction / Macroautophagy / lysosome organization / positive regulation of transforming growth factor beta receptor signaling pathway / RHOJ GTPase cycle / RHOQ GTPase cycle / mTORC1-mediated signalling / tertiary granule membrane / CDC42 GTPase cycle / hemopoiesis / ficolin-1-rich granule membrane / RHOH GTPase cycle / negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / centriolar satellite / RHOG GTPase cycle / TOR signaling / regulation of receptor recycling / positive regulation of TOR signaling / RAC2 GTPase cycle / RAC3 GTPase cycle / response to amino acid / cellular response to nutrient levels / positive regulation of autophagy / specific granule membrane / positive regulation of intrinsic apoptotic signaling pathway / protein-membrane adaptor activity / energy homeostasis / epithelial cell proliferation / Regulation of PTEN gene transcription / tumor necrosis factor-mediated signaling pathway / RAC1 GTPase cycle / positive regulation of TORC1 signaling / ERK1 and ERK2 cascade / phosphatidylinositol 3-kinase/protein kinase B signal transduction / cellular response to starvation / cellular response to amino acid starvation / intrinsic apoptotic signaling pathway / GTPase activator activity / viral genome replication / negative regulation of autophagy / cellular response to amino acid stimulus / transforming growth factor beta receptor signaling pathway / RNA splicing / negative regulation of cysteine-type endopeptidase activity involved in apoptotic process / guanyl-nucleotide exchange factor activity / cholesterol homeostasis / positive regulation of interleukin-8 production / regulation of cell growth / TP53 Regulates Metabolic Genes / phosphoprotein binding / 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 / regulation of protein phosphorylation / response to virus / MAP2K and MAPK activation / positive regulation of protein-containing complex assembly / cilium / negative regulation of ERK1 and ERK2 cascade / mitotic spindle / positive regulation of protein localization to nucleus / GDP binding / negative regulation of epithelial cell proliferation 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: 8.1 Å | |||||||||
![]() | Yokom AL / Fromm SA / Hurley JH | |||||||||
資金援助 | ![]()
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![]() | ![]() タイトル: Structural mechanism of a Rag GTPase activation checkpoint by the lysosomal folliculin complex. 著者: Rosalie E Lawrence / Simon A Fromm / Yangxue Fu / Adam L Yokom / Do Jin Kim / Ashley M Thelen / Lindsey N Young / Chun-Yan Lim / Avi J Samelson / James H Hurley / Roberto Zoncu / ![]() 要旨: The tumor suppressor folliculin (FLCN) enables nutrient-dependent activation of the mechanistic target of rapamycin complex 1 (mTORC1) protein kinase via its guanosine triphosphatase (GTPase) ...The tumor suppressor folliculin (FLCN) enables nutrient-dependent activation of the mechanistic target of rapamycin complex 1 (mTORC1) protein kinase via its guanosine triphosphatase (GTPase) activating protein (GAP) activity toward the GTPase RagC. Concomitant with mTORC1 inactivation by starvation, FLCN relocalizes from the cytosol to lysosomes. To determine the lysosomal function of FLCN, we reconstituted the human lysosomal FLCN complex (LFC) containing FLCN, its partner FLCN-interacting protein 2 (FNIP2), and the RagA:RagC GTPases as they exist in the starved state with their lysosomal anchor Ragulator complex and determined its cryo-electron microscopy structure to 3.6 angstroms. The RagC-GAP activity of FLCN was inhibited within the LFC, owing to displacement of a catalytically required arginine in FLCN from the RagC nucleotide. Disassembly of the LFC and release of the RagC-GAP activity of FLCN enabled mTORC1-dependent regulation of the master regulator of lysosomal biogenesis, transcription factor E3, implicating the LFC as a checkpoint in mTORC1 signaling. | |||||||||
履歴 |
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構造の表示
ムービー |
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構造ビューア | EMマップ: ![]() ![]() ![]() |
添付画像 |
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ダウンロードとリンク
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マップデータ | ![]() | 1.6 MB | ![]() | |
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ヘッダ (付随情報) | ![]() ![]() | 12.9 KB 12.9 KB | 表示 表示 | ![]() |
画像 | ![]() | 43.1 KB | ||
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
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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 | em-volume_P1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 1.149 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
密度 |
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対称性 | 空間群: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
詳細 | EMDB XML:
CCP4マップ ヘッダ情報:
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-添付データ
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試料の構成要素
-全体 : active RagA-RagC-Ragulator Complex
全体 | 名称: active RagA-RagC-Ragulator Complex |
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要素 |
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-超分子 #1: active RagA-RagC-Ragulator Complex
超分子 | 名称: active RagA-RagC-Ragulator Complex / タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: #1-#9 詳細: RagA bound to GTP; RagC bound to XDP RagC has T90N and D181N mutations |
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由来(天然) | 生物種: ![]() |
組換発現 | 生物種: ![]() ![]() 組換株: Sf9 |
分子量 | 理論値: 150 KDa |
-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
濃度 | 0.5 mg/mL | |||||||||||||||
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緩衝液 | pH: 7.4 構成要素:
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グリッド | モデル: C-flat-2/1 / 材質: COPPER / メッシュ: 400 / 支持フィルム - 材質: CARBON / 支持フィルム - トポロジー: HOLEY | |||||||||||||||
凍結 | 凍結剤: ETHANE / チャンバー内湿度: 90 % / チャンバー内温度: 298 K / 装置: FEI VITROBOT MARK IV |
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電子顕微鏡法
顕微鏡 | FEI TITAN KRIOS |
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特殊光学系 | エネルギーフィルター - スリット幅: 20 eV |
撮影 | フィルム・検出器のモデル: GATAN K2 SUMMIT (4k x 4k) 検出モード: SUPER-RESOLUTION / 平均露光時間: 8.0 sec. / 平均電子線量: 48.0 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: OTHER / 撮影モード: BRIGHT FIELD / Cs: 2.7 mm |
試料ステージ | 試料ホルダーモデル: FEI TITAN KRIOS AUTOGRID HOLDER ホルダー冷却材: NITROGEN |
実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |