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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: PDB / ID: 6bcu | ||||||
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タイトル | Cryo-EM structure of the activated RHEB-mTORC1 refined to 3.4 angstrom | ||||||
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![]() | TRANSFERASE / PIKK | ||||||
機能・相同性 | ![]() regulation of type B pancreatic cell development / 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 / Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S / positive regulation of wound healing, spreading of epidermal cells / eukaryotic initiation factor 4E binding ...regulation of type B pancreatic cell development / 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 / Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S / positive regulation of wound healing, spreading of epidermal cells / eukaryotic initiation factor 4E binding / TORC2 signaling / TORC2 complex / regulation of membrane permeability / 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 / calcineurin-NFAT signaling cascade / positive regulation of odontoblast differentiation / regulation of osteoclast differentiation / RNA polymerase III type 3 promoter sequence-specific DNA binding / positive regulation of keratinocyte migration / regulation of lysosome organization / MTOR signalling / Amino acids regulate mTORC1 / cellular response to nutrient / energy reserve metabolic process / cellular response to L-leucine / regulation of autophagosome assembly / Energy dependent regulation of mTOR by LKB1-AMPK / TORC1 signaling / ruffle organization / serine/threonine protein kinase complex / cellular response to methionine / negative regulation of cell size / positive regulation of osteoclast differentiation / positive regulation of ubiquitin-dependent protein catabolic process / inositol hexakisphosphate binding / cellular response to osmotic stress / anoikis / negative regulation of protein localization to nucleus / cardiac muscle cell development / negative regulation of cold-induced thermogenesis / negative regulation of calcineurin-NFAT signaling cascade / regulation of myelination / positive regulation of transcription by RNA polymerase III / negative regulation of macroautophagy / small GTPase-mediated signal transduction / Macroautophagy / positive regulation of myotube differentiation / regulation of cell size / positive regulation of actin filament polymerization / Constitutive Signaling by AKT1 E17K in Cancer / germ cell development / TOR signaling / behavioral response to pain / mTORC1-mediated signalling / oligodendrocyte differentiation / positive regulation of oligodendrocyte differentiation / positive regulation of translational initiation / protein kinase activator activity / social behavior / protein serine/threonine kinase inhibitor activity / CD28 dependent PI3K/Akt signaling / positive regulation of TOR signaling / HSF1-dependent transactivation / regulation of macroautophagy / enzyme-substrate adaptor activity / positive regulation of G1/S transition of mitotic cell cycle / response to amino acid / 'de novo' pyrimidine nucleobase biosynthetic process / positive regulation of epithelial to mesenchymal transition / heart morphogenesis / vascular endothelial cell response to laminar fluid shear stress / neuronal action potential / positive regulation of lipid biosynthetic process / cellular response to nutrient levels / regulation of cellular response to heat / positive regulation of lamellipodium assembly / cardiac muscle contraction / phagocytic vesicle / T cell costimulation / positive regulation of stress fiber assembly / translation initiation factor binding / translation repressor activity / positive regulation of endothelial cell proliferation / 14-3-3 protein binding / cytoskeleton organization / negative regulation of translational initiation / positive regulation of TORC1 signaling / endomembrane system / negative regulation of autophagy / negative regulation of insulin receptor signaling pathway / positive regulation of mitotic cell cycle / cellular response to amino acid starvation / cellular response to starvation / positive regulation of glycolytic process 類似検索 - 分子機能 | ||||||
生物種 | ![]() | ||||||
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: 3.8 Å | ||||||
![]() | Pavletich, N.P. / Yang, H. | ||||||
資金援助 | ![]()
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![]() | ![]() タイトル: Mechanisms of mTORC1 activation by RHEB and inhibition by PRAS40. 著者: Haijuan Yang / Xiaolu Jiang / Buren Li / Hyo J Yang / Meredith Miller / Angela Yang / Ankita Dhar / Nikola P Pavletich / ![]() 要旨: The mechanistic target of rapamycin complex 1 (mTORC1) controls cell growth and metabolism in response to nutrients, energy levels, and growth factors. It contains the atypical kinase mTOR and the ...The mechanistic target of rapamycin complex 1 (mTORC1) controls cell growth and metabolism in response to nutrients, energy levels, and growth factors. It contains the atypical kinase mTOR and the RAPTOR subunit that binds to the Tor signalling sequence (TOS) motif of substrates and regulators. mTORC1 is activated by the small GTPase RHEB (Ras homologue enriched in brain) and inhibited by PRAS40. Here we present the 3.0 ångström cryo-electron microscopy structure of mTORC1 and the 3.4 ångström structure of activated RHEB-mTORC1. RHEB binds to mTOR distally from the kinase active site, yet causes a global conformational change that allosterically realigns active-site residues, accelerating catalysis. Cancer-associated hyperactivating mutations map to structural elements that maintain the inactive state, and we provide biochemical evidence that they mimic RHEB relieving auto-inhibition. We also present crystal structures of RAPTOR-TOS motif complexes that define the determinants of TOS recognition, of an mTOR FKBP12-rapamycin-binding (FRB) domain-substrate complex that establishes a second substrate-recruitment mechanism, and of a truncated mTOR-PRAS40 complex that reveals PRAS40 inhibits both substrate-recruitment sites. These findings help explain how mTORC1 selects its substrates, how its kinase activity is controlled, and how it is activated by cancer-associated mutations. | ||||||
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構造の表示
ムービー |
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構造ビューア | 分子: ![]() ![]() |
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ダウンロードとリンク
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ダウンロード
PDBx/mmCIF形式 | ![]() | 2.7 MB | 表示 | ![]() |
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PDB形式 | ![]() | 表示 | ![]() | |
PDBx/mmJSON形式 | ![]() | ツリー表示 | ![]() | |
その他 | ![]() |
-検証レポート
文書・要旨 | ![]() | 1.3 MB | 表示 | ![]() |
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文書・詳細版 | ![]() | 1.3 MB | 表示 | |
XML形式データ | ![]() | 171.8 KB | 表示 | |
CIF形式データ | ![]() | 270 KB | 表示 | |
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-関連構造データ
関連構造データ | ![]() 7086MC ![]() 7087C ![]() 5wbhC ![]() 5wbiC ![]() 5wbjC ![]() 5wbkC ![]() 5wblC ![]() 5wbuC ![]() 5wbyC ![]() 6bcxC M: このデータのモデリングに利用したマップデータ C: 同じ文献を引用 ( |
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類似構造データ |
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リンク
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集合体
登録構造単位 | ![]()
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要素
-タンパク質 , 5種, 10分子 ABDEWYXZSR
#1: タンパク質 | 分子量: 287399.125 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() 参照: UniProt: P42345, non-specific serine/threonine protein kinase #2: 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) ![]() ![]() #3: タンパク質 | 分子量: 150197.000 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() #4: タンパク質 | 分子量: 12951.344 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() #5: タンパク質 | 分子量: 20877.826 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() |
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-非ポリマー , 3種, 10分子 




#6: 化合物 | #7: 化合物 | ChemComp-MG / #8: 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 |
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試料調製
構成要素 | 名称: active complex / タイプ: COMPLEX / Entity ID: #1-#5 / 由来: RECOMBINANT |
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分子量 | 実験値: NO |
由来(天然) | 生物種: ![]() |
由来(組換発現) | 生物種: ![]() |
緩衝液 | pH: 8 |
試料 | 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES |
急速凍結 | 凍結剤: ETHANE |
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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 |
電子銃 | 電子線源: ![]() |
電子レンズ | モード: BRIGHT FIELD |
撮影 | 電子線照射量: 56 e/Å2 フィルム・検出器のモデル: GATAN K2 SUMMIT (4k x 4k) |
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解析
ソフトウェア | 名称: REFMAC / バージョン: 5.8.0158 / 分類: 精密化 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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EMソフトウェア |
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CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
対称性 | 点対称性: C2 (2回回転対称) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
3次元再構成 | 解像度: 3.8 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 198237 / 対称性のタイプ: POINT | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
原子モデル構築 | プロトコル: AB INITIO MODEL | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
精密化 | 解像度: 3.8→3.8 Å / Cor.coef. Fo:Fc: 0.869 / SU B: 44.652 / SU ML: 0.268 / ESU R: 0.473 立体化学のターゲット値: MAXIMUM LIKELIHOOD WITH PHASES 詳細: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
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溶媒の処理 | イオンプローブ半径: 0.9 Å / 減衰半径: 0.9 Å / VDWプローブ半径: 1 Å / 溶媒モデル: MASK | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
原子変位パラメータ | Biso mean: 40.812 Å2
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精密化ステップ | サイクル: 1 / 合計: 59662 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
拘束条件 |
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