+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 5flc | ||||||
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タイトル | Architecture of human mTOR Complex 1 - 5.9 Angstrom reconstruction | ||||||
要素 |
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キーワード | TRANSFERASE (転移酵素) / RAPAMYCIN (ラパマイシン) / MTORC1 (MTORC1) | ||||||
機能・相同性 | 機能・相同性情報 RNA polymerase III type 2 promoter sequence-specific DNA binding / positive regulation of cytoplasmic translational initiation / RNA polymerase III type 1 promoter sequence-specific DNA binding / positive regulation of pentose-phosphate shunt / T-helper 1 cell lineage commitment / regulation of locomotor rhythm / positive regulation of wound healing, spreading of epidermal cells / cellular response to leucine starvation / TFIIIC-class transcription factor complex binding / TORC2 complex ...RNA polymerase III type 2 promoter sequence-specific DNA binding / positive regulation of cytoplasmic translational initiation / RNA polymerase III type 1 promoter sequence-specific DNA binding / positive regulation of pentose-phosphate shunt / T-helper 1 cell lineage commitment / regulation of locomotor rhythm / positive regulation of wound healing, spreading of epidermal cells / cellular response to leucine starvation / TFIIIC-class transcription factor complex binding / TORC2 complex / heart valve morphogenesis / regulation of membrane permeability / negative regulation of lysosome organization / RNA polymerase III type 3 promoter sequence-specific DNA binding / TORC1 complex / positive regulation of transcription of nucleolar large rRNA by RNA polymerase I / calcineurin-NFAT signaling cascade / regulation of autophagosome assembly / TORC1 signaling / voluntary musculoskeletal movement / regulation of osteoclast differentiation / positive regulation of keratinocyte migration / cellular response to L-leucine / MTOR signalling / Amino acids regulate mTORC1 / cellular response to nutrient / energy reserve metabolic process / Energy dependent regulation of mTOR by LKB1-AMPK / nucleus localization / ruffle organization / negative regulation of cell size / cellular response to osmotic stress / anoikis / cardiac muscle cell development / positive regulation of transcription by RNA polymerase III / negative regulation of protein localization to nucleus / regulation of myelination / negative regulation of calcineurin-NFAT signaling cascade / オートファジー / regulation of cell size / negative regulation of macroautophagy / lysosome organization / positive regulation of oligodendrocyte differentiation / positive regulation of actin filament polymerization / positive regulation of myotube differentiation / behavioral response to pain / MTOR / oligodendrocyte differentiation / mTORC1-mediated signalling / germ cell development / Constitutive Signaling by AKT1 E17K in Cancer / cellular response to nutrient levels / CD28 dependent PI3K/Akt signaling / positive regulation of phosphoprotein phosphatase activity / positive regulation of translational initiation / neuronal action potential / HSF1-dependent transactivation / positive regulation of TOR signaling / positive regulation of epithelial to mesenchymal transition / regulation of macroautophagy / 細胞内膜系 / 'de novo' pyrimidine nucleobase biosynthetic process / response to amino acid / positive regulation of lipid biosynthetic process / phagocytic vesicle / positive regulation of lamellipodium assembly / heart morphogenesis / regulation of cellular response to heat / cytoskeleton organization / cardiac muscle contraction / positive regulation of stress fiber assembly / cellular response to amino acid starvation / T cell costimulation / cellular response to starvation / positive regulation of glycolytic process / protein serine/threonine kinase activator activity / response to nutrient levels / post-embryonic development / response to nutrient / negative regulation of autophagy / positive regulation of translation / VEGFR2 mediated vascular permeability / Regulation of PTEN gene transcription / regulation of signal transduction by p53 class mediator / regulation of cell growth / regulation of actin cytoskeleton organization / cellular response to amino acid stimulus / TP53 Regulates Metabolic Genes / オートファジー / phosphoprotein binding / protein catabolic process / protein destabilization / multicellular organism growth / regulation of circadian rhythm / PML body / cellular response to insulin stimulus / rhythmic process / positive regulation of peptidyl-tyrosine phosphorylation / Regulation of TP53 Degradation / ribosome binding 類似検索 - 分子機能 | ||||||
生物種 | HOMO SAPIENS (ヒト) SPODOPTERA FRUGIPERDA (ツマジロクサヨトウ) | ||||||
手法 | 電子顕微鏡法 / 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 5.9 Å | ||||||
データ登録者 | Aylett, C.H.S. / Sauer, E. / Imseng, S. / Boehringer, D. / Hall, M.N. / Ban, N. / Maier, T. | ||||||
引用 | ジャーナル: Science / 年: 2016 タイトル: Architecture of human mTOR complex 1. 著者: Christopher H S Aylett / Evelyn Sauer / Stefan Imseng / Daniel Boehringer / Michael N Hall / Nenad Ban / Timm Maier / 要旨: Target of rapamycin (TOR), a conserved protein kinase and central controller of cell growth, functions in two structurally and functionally distinct complexes: TORC1 and TORC2. Dysregulation of ...Target of rapamycin (TOR), a conserved protein kinase and central controller of cell growth, functions in two structurally and functionally distinct complexes: TORC1 and TORC2. Dysregulation of mammalian TOR (mTOR) signaling is implicated in pathologies that include diabetes, cancer, and neurodegeneration. We resolved the architecture of human mTORC1 (mTOR with subunits Raptor and mLST8) bound to FK506 binding protein (FKBP)-rapamycin, by combining cryo-electron microscopy at 5.9 angstrom resolution with crystallographic studies of Chaetomium thermophilum Raptor at 4.3 angstrom resolution. The structure explains how FKBP-rapamycin and architectural elements of mTORC1 limit access to the recessed active site. Consistent with a role in substrate recognition and delivery, the conserved amino-terminal domain of Raptor is juxtaposed to the kinase active site. | ||||||
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 | 分子: MolmilJmol/JSmol |
-ダウンロードとリンク
-ダウンロード
PDBx/mmCIF形式 | 5flc.cif.gz | 1010.8 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb5flc.ent.gz | 832.4 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 5flc.json.gz | ツリー表示 | PDBx/mmJSON形式 | |
その他 | その他のダウンロード |
-検証レポート
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/fl/5flc ftp://data.pdbj.org/pub/pdb/validation_reports/fl/5flc | HTTPS FTP |
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-関連構造データ
-リンク
-集合体
登録構造単位 |
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1 |
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-要素
-SERINE/THREONINE-PROTEIN KINASE ... , 3種, 6分子 1324BF
#1: タンパク質 | 分子量: 52357.672 Da / 分子数: 2 / 断片: HORN DOMAIN / 由来タイプ: 組換発現 / 由来: (組換発現) HOMO SAPIENS (ヒト) / 細胞株 (発現宿主): Sf21 発現宿主: SPODOPTERA FRUGIPERDA (ツマジロクサヨトウ) 参照: non-specific serine/threonine protein kinase #2: タンパク質 | 分子量: 31081.197 Da / 分子数: 2 / 断片: BRIDGE DOMAIN / 由来タイプ: 組換発現 / 由来: (組換発現) HOMO SAPIENS (ヒト) / 細胞株 (発現宿主): Sf21 発現宿主: SPODOPTERA FRUGIPERDA (ツマジロクサヨトウ) 参照: non-specific serine/threonine protein kinase #4: タンパク質 | 分子量: 134036.641 Da / 分子数: 2 / 断片: FAT AND PIKK DOMAINS / 由来タイプ: 組換発現 / 由来: (組換発現) HOMO SAPIENS (ヒト) / 細胞株 (発現宿主): Sf21 発現宿主: SPODOPTERA FRUGIPERDA (ツマジロクサヨトウ) 参照: UniProt: P42345, non-specific serine/threonine protein kinase |
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-タンパク質 , 3種, 6分子 AECGDH
#3: タンパク質 | 分子量: 87589.977 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) HOMO SAPIENS (ヒト) / 細胞株 (発現宿主): Sf21 発現宿主: SPODOPTERA FRUGIPERDA (ツマジロクサヨトウ) #5: タンパク質 | 分子量: 9124.238 Da / 分子数: 2 / 由来タイプ: 天然 由来: (天然) SPODOPTERA FRUGIPERDA (ツマジロクサヨトウ) #6: タンパク質 | 分子量: 35910.090 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) HOMO SAPIENS (ヒト) / 細胞株 (発現宿主): Sf21 発現宿主: SPODOPTERA FRUGIPERDA (ツマジロクサヨトウ) 参照: UniProt: Q9BVC4 |
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-非ポリマー , 1種, 2分子
#7: 化合物 |
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-実験情報
-実験
実験 | 手法: 電子顕微鏡法 |
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EM実験 | 試料の集合状態: PARTICLE / 3次元再構成法: 単粒子再構成法 |
-試料調製
構成要素 | 名称: HUMAN MTOR COMPLEX 1MTORC1 / タイプ: COMPLEX |
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緩衝液 | 名称: 100 MM NACL, 10 MM NABICINE, 1 MM TCEP / pH: 8 / 詳細: 100 MM NACL, 10 MM NABICINE, 1 MM TCEP |
試料 | 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES |
試料支持 | 詳細: CARBON |
急速凍結 | 装置: FEI VITROBOT MARK I / 凍結剤: ETHANE 詳細: VITRIFICATION 1 -- CRYOGEN- ETHANE, HUMIDITY- 100, TEMPERATURE- 120, INSTRUMENT- FEI VITROBOT MARK I, METHOD- 4 SECOND BLOTTING, |
-電子顕微鏡撮影
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |
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顕微鏡 | モデル: FEI TITAN KRIOS / 日付: 2015年5月5日 |
電子銃 | 電子線源: FIELD EMISSION GUN / 加速電圧: 300 kV / 照射モード: FLOOD BEAM |
電子レンズ | モード: BRIGHT FIELDBright-field microscopy / 倍率(公称値): 59000 X / 倍率(補正後): 100719 X / 最大 デフォーカス(公称値): 4000 nm / 最小 デフォーカス(公称値): 1900 nm / Cs: 2.7 mm |
試料ホルダ | 温度: 100 K |
撮影 | 電子線照射量: 25 e/Å2 フィルム・検出器のモデル: FEI FALCON II (4k x 4k) |
-解析
EMソフトウェア |
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CTF補正 | 詳細: EACH IMAGE | ||||||||||||||||
対称性 | 点対称性: C2 (2回回転対称) | ||||||||||||||||
3次元再構成 | 手法: MAXIMUM A POSTERIORI PROJECTION MATCHING / 解像度: 5.9 Å / 粒子像の数: 309792 / ピクセルサイズ(公称値): 1.39 Å / ピクセルサイズ(実測値): 1.39 Å 詳細: THE UNK CHAINS (A, E, C, G, 1-4) CORRESPONDING TO RAPTOR (A,E), SF FKBP AND RAPAMYCIN (C,G) AND THE N-TERMINAL HEAT REPEATS OF MTOR (1-4), HAVE BEEN NUMBERED FROM 100 AT EACH BREAK TO ...詳細: THE UNK CHAINS (A, E, C, G, 1-4) CORRESPONDING TO RAPTOR (A,E), SF FKBP AND RAPAMYCIN (C,G) AND THE N-TERMINAL HEAT REPEATS OF MTOR (1-4), HAVE BEEN NUMBERED FROM 100 AT EACH BREAK TO INDICATE LACK OF SEQUENCE - DENSITY CERTAINTY. CHAINS 1-4 CORRESPOND TO THE N-TERMINAL HEAT REPEAT DOMAINS OF MTOR. WE PROPOSE A TOPOLOGY IN THE CORRESPONDING PAPER (1-2-B AND 3-4-F), BUT GIVEN THE FACT THAT THEIR TOPOLOGY CANNOT BE ASSIGNED DEFINITIVELY THEY ARE REPRESENTED AS A SEPARATE CHAIN FOR EACH DOMAIN. THE FITTING OF CRYSTAL STRUCTURES FOR THE MTOR FAT AND PIKK DOMAINS, MLST8, RAPTOR AND FKBP ALLOWS THEIR DENSITY TO BE ASSIGNED DEFINITIVELY, AND THEIR CHAINS ARE THEREFORE LETTERED. SUBMISSION BASED ON EXPERIMENTAL DATA FROM EMDB EMD-3213. (DEPOSITION ID: 13912). 対称性のタイプ: POINT | ||||||||||||||||
原子モデル構築 | プロトコル: RIGID BODY FIT / Target criteria: FSC / 詳細: METHOD--RIGID BODY | ||||||||||||||||
精密化 | 最高解像度: 5.9 Å | ||||||||||||||||
精密化ステップ | サイクル: LAST / 最高解像度: 5.9 Å
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