+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-20814 | ||||||||||||||||||||||||
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タイトル | Cryo-EM structure of the FLCN-FNIP2-Rag-Ragulator complex | ||||||||||||||||||||||||
マップデータ | |||||||||||||||||||||||||
試料 |
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機能・相同性 | 機能・相同性情報 negative regulation of cell proliferation involved in kidney development / cell proliferation involved in kidney development / negative regulation of post-translational protein modification / 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 / cell proliferation involved in kidney development / negative regulation of post-translational protein modification / 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 / regulation of pro-B cell differentiation / negative regulation of lysosome organization / protein localization to lysosome / regulation of TOR signaling / TORC1 signaling / endosome organization / fibroblast migration / lysosome localization / Amino acids regulate mTORC1 / ATPase inhibitor activity / MTOR signalling / Energy dependent regulation of mTOR by LKB1-AMPK / protein localization to membrane / kinase activator activity / negative regulation of TOR signaling / enzyme inhibitor activity / negative regulation of glycolytic process / cell-cell junction assembly / enzyme-substrate adaptor activity / negative regulation of cold-induced thermogenesis / negative regulation of Rho protein signal transduction / azurophil granule membrane / endosomal transport / small GTPase-mediated signal transduction / regulation of cell size / lysosome organization / Macroautophagy / positive regulation of transforming growth factor beta receptor signaling pathway / RHOJ GTPase cycle / RHOQ GTPase cycle / mTORC1-mediated signalling / tertiary granule membrane / hemopoiesis / CDC42 GTPase cycle / ficolin-1-rich granule membrane / RHOH GTPase cycle / centriolar satellite / negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / RHOG GTPase cycle / positive regulation of TOR signaling / regulation of receptor recycling / response to amino acid / RAC2 GTPase cycle / TOR signaling / RAC3 GTPase cycle / cellular response to nutrient levels / specific granule membrane / positive regulation of intrinsic apoptotic signaling pathway / positive regulation of autophagy / protein-membrane adaptor activity / energy homeostasis / tumor necrosis factor-mediated signaling pathway / RAC1 GTPase cycle / positive regulation of TORC1 signaling / intrinsic apoptotic signaling pathway / cellular response to amino acid starvation / ERK1 and ERK2 cascade / cellular response to starvation / phosphatidylinositol 3-kinase/protein kinase B signal transduction / GTPase activator activity / negative regulation of autophagy / viral genome replication / RNA splicing / transforming growth factor beta receptor signaling pathway / : / epithelial cell proliferation / guanyl-nucleotide exchange factor activity / cholesterol homeostasis / Regulation of PTEN gene transcription / positive regulation of interleukin-8 production / regulation of cell growth / cellular response to amino acid stimulus / TP53 Regulates Metabolic Genes / phosphoprotein binding / positive regulation of protein-containing complex assembly / regulation of protein phosphorylation / MAP2K and MAPK activation / response to virus / cilium / mitotic spindle / negative regulation of ERK1 and ERK2 cascade / positive regulation of protein localization to nucleus / intrinsic apoptotic signaling pathway in response to DNA damage / negative regulation of epithelial cell proliferation / GDP binding 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: 3.31 Å | ||||||||||||||||||||||||
データ登録者 | Shen K / Rogala KB / Yu ZH / Sabatini DM | ||||||||||||||||||||||||
資金援助 | 米国, 7件
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引用 | ジャーナル: Cell / 年: 2019 タイトル: Cryo-EM Structure of the Human FLCN-FNIP2-Rag-Ragulator Complex. 著者: Kuang Shen / Kacper B Rogala / Hui-Ting Chou / Rick K Huang / Zhiheng Yu / David M Sabatini / 要旨: mTORC1 controls anabolic and catabolic processes in response to nutrients through the Rag GTPase heterodimer, which is regulated by multiple upstream protein complexes. One such regulator, FLCN- ...mTORC1 controls anabolic and catabolic processes in response to nutrients through the Rag GTPase heterodimer, which is regulated by multiple upstream protein complexes. One such regulator, FLCN-FNIP2, is a GTPase activating protein (GAP) for RagC/D, but despite its important role, how it activates the Rag GTPase heterodimer remains unknown. We used cryo-EM to determine the structure of FLCN-FNIP2 in a complex with the Rag GTPases and Ragulator. FLCN-FNIP2 adopts an extended conformation with two pairs of heterodimerized domains. The Longin domains heterodimerize and contact both nucleotide binding domains of the Rag heterodimer, while the DENN domains interact at the distal end of the structure. Biochemical analyses reveal a conserved arginine on FLCN as the catalytic arginine finger and lead us to interpret our structure as an on-pathway intermediate. These data reveal features of a GAP-GTPase interaction and the structure of a critical component of the nutrient-sensing mTORC1 pathway. | ||||||||||||||||||||||||
履歴 |
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-構造の表示
ムービー |
ムービービューア |
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構造ビューア | EMマップ: SurfViewMolmilJmol/JSmol |
添付画像 |
-ダウンロードとリンク
-EMDBアーカイブ
マップデータ | emd_20814.map.gz | 166.7 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-20814-v30.xml emd-20814.xml | 22.1 KB 22.1 KB | 表示 表示 | EMDBヘッダ |
画像 | emd_20814.png | 54.6 KB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-20814 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-20814 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_20814_validation.pdf.gz | 517 KB | 表示 | EMDB検証レポート |
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文書・詳細版 | emd_20814_full_validation.pdf.gz | 516.6 KB | 表示 | |
XML形式データ | emd_20814_validation.xml.gz | 6.7 KB | 表示 | |
CIF形式データ | emd_20814_validation.cif.gz | 7.7 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-20814 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-20814 | HTTPS FTP |
-関連構造データ
-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 |
-マップ
ファイル | ダウンロード / ファイル: emd_20814.map.gz / 形式: CCP4 / 大きさ: 178 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 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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
-試料の構成要素
+全体 : Nonameric complex of FLCN-FNIP2 with its substrate Rag GTPases an...
+超分子 #1: Nonameric complex of FLCN-FNIP2 with its substrate Rag GTPases an...
+分子 #1: Folliculin
+分子 #2: Ragulator complex protein LAMTOR3
+分子 #3: Ragulator complex protein LAMTOR2
+分子 #4: Ragulator complex protein LAMTOR5
+分子 #5: Ragulator complex protein LAMTOR4
+分子 #6: Ragulator complex protein LAMTOR1
+分子 #7: Ras-related GTP-binding protein A
+分子 #8: Ras-related GTP-binding protein C
+分子 #9: Folliculin-interacting protein 2
+分子 #10: GUANOSINE-5'-DIPHOSPHATE
+分子 #11: PHOSPHOAMINOPHOSPHONIC ACID-GUANYLATE ESTER
+分子 #12: MAGNESIUM ION
-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 |
-試料調製
濃度 | 8 mg/mL |
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緩衝液 | pH: 7.4 |
凍結 | 凍結剤: ETHANE |
-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 K2 BASE (4k x 4k) 平均電子線量: 59.2 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 |
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |
-画像解析
最終 再構成 | 想定した対称性 - 点群: C1 (非対称) / 解像度のタイプ: BY AUTHOR / 解像度: 3.31 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 使用した粒子像数: 126984 |
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初期 角度割当 | タイプ: NOT APPLICABLE |
最終 角度割当 | タイプ: NOT APPLICABLE |