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基本情報
登録情報 | データベース: PDB / ID: 7pe8 | ||||||
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タイトル | cryo-EM structure of DEPTOR bound to human mTOR complex 2, focussed on one protomer | ||||||
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![]() | SIGNALING PROTEIN / DEPTOR / mTOR / regulator / inhibitor / mTORC2 / DEP-domain / PDZ-domain | ||||||
機能・相同性 | ![]() negative regulation of TORC2 signaling / regulation of extrinsic apoptotic signaling pathway / TORC2 signaling / regulation of peptidyl-serine phosphorylation / positive regulation of cytoplasmic translational initiation / positive regulation of pentose-phosphate shunt / RNA polymerase III type 1 promoter sequence-specific DNA binding / RNA polymerase III type 2 promoter sequence-specific DNA binding / T-helper 1 cell lineage commitment / regulation of locomotor rhythm ...negative regulation of TORC2 signaling / regulation of extrinsic apoptotic signaling pathway / TORC2 signaling / regulation of peptidyl-serine phosphorylation / positive regulation of cytoplasmic translational initiation / positive regulation of pentose-phosphate shunt / RNA polymerase III type 1 promoter sequence-specific DNA binding / RNA polymerase III type 2 promoter sequence-specific DNA binding / T-helper 1 cell lineage commitment / regulation of locomotor rhythm / positive regulation of wound healing, spreading of epidermal cells / cellular response to leucine starvation / regulation of membrane permeability / TFIIIC-class transcription factor complex binding / heart valve morphogenesis / negative regulation of lysosome organization / RNA polymerase III type 3 promoter sequence-specific DNA binding / TORC2 complex / TORC1 complex / positive regulation of transcription of nucleolar large rRNA by RNA polymerase I / regulation of cellular response to oxidative stress / regulation of autophagosome assembly / calcineurin-NFAT signaling cascade / nucleus localization / 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 / phosphatidic acid binding / Energy dependent regulation of mTOR by LKB1-AMPK / negative regulation of cell size / ruffle organization / protein serine/threonine kinase inhibitor activity / phosphatidylinositol-3,4-bisphosphate binding / negative regulation of Ras protein signal transduction / cellular response to osmotic stress / negative regulation of protein localization to nucleus / anoikis / cardiac muscle cell development / negative regulation of TOR signaling / phosphatidylinositol-3,5-bisphosphate binding / regulation of establishment of cell polarity / embryo development ending in birth or egg hatching / positive regulation of transcription by RNA polymerase III / negative regulation of calcineurin-NFAT signaling cascade / regulation of myelination / regulation of cell size / Macroautophagy / positive regulation of oligodendrocyte differentiation / negative regulation of macroautophagy / positive regulation of actin filament polymerization / lysosome organization / positive regulation of myotube differentiation / protein kinase inhibitor activity / behavioral response to pain / oligodendrocyte differentiation / regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / Constitutive Signaling by AKT1 E17K in Cancer / mTORC1-mediated signalling / germ cell development / CD28 dependent PI3K/Akt signaling / cellular response to nutrient levels / phosphatidylinositol-3,4,5-trisphosphate binding / positive regulation of phosphoprotein phosphatase activity / HSF1-dependent transactivation / positive regulation of TOR signaling / TOR signaling / neuronal action potential / positive regulation of translational initiation / response to amino acid / regulation of macroautophagy / endomembrane system / 'de novo' pyrimidine nucleobase biosynthetic process / positive regulation of autophagy / positive regulation of lamellipodium assembly / positive regulation of epithelial to mesenchymal transition / positive regulation of lipid biosynthetic process / heart morphogenesis / cardiac muscle contraction / regulation of cellular response to heat / positive regulation of stress fiber assembly / negative regulation of TORC1 signaling / positive regulation of endothelial cell proliferation / cytoskeleton organization / T cell costimulation / substantia nigra development / phosphatidylinositol-4,5-bisphosphate binding / cellular response to amino acid starvation / phagocytic vesicle / positive regulation of glycolytic process / cellular response to starvation / negative regulation of autophagy / protein serine/threonine kinase activator activity / response to nutrient levels / response to nutrient 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: 3.2 Å | ||||||
![]() | Waelchli, M. / Maier, T. | ||||||
資金援助 | ![]()
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![]() | ![]() タイトル: Regulation of human mTOR complexes by DEPTOR. 著者: Matthias Wälchli / Karolin Berneiser / Francesca Mangia / Stefan Imseng / Louise-Marie Craigie / Edward Stuttfeld / Michael N Hall / Timm Maier / ![]() 要旨: The vertebrate-specific DEP domain-containing mTOR interacting protein (DEPTOR), an oncoprotein or tumor suppressor, has important roles in metabolism, immunity, and cancer. It is the only protein ...The vertebrate-specific DEP domain-containing mTOR interacting protein (DEPTOR), an oncoprotein or tumor suppressor, has important roles in metabolism, immunity, and cancer. It is the only protein that binds and regulates both complexes of mammalian target of rapamycin (mTOR), a central regulator of cell growth. Biochemical analysis and cryo-EM reconstructions of DEPTOR bound to human mTOR complex 1 (mTORC1) and mTORC2 reveal that both structured regions of DEPTOR, the PDZ domain and the DEP domain tandem (DEPt), are involved in mTOR interaction. The PDZ domain binds tightly with mildly activating effect, but then acts as an anchor for DEPt association that allosterically suppresses mTOR activation. The binding interfaces of the PDZ domain and DEPt also support further regulation by other signaling pathways. A separate, substrate-like mode of interaction for DEPTOR phosphorylation by mTOR complexes rationalizes inhibition of non-stimulated mTOR activity at higher DEPTOR concentrations. The multifaceted interplay between DEPTOR and mTOR provides a basis for understanding the divergent roles of DEPTOR in physiology and opens new routes for targeting the mTOR-DEPTOR interaction in disease. | ||||||
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構造の表示
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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 | ![]() | 697.6 KB | 表示 | ![]() |
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PDB形式 | ![]() | 547.8 KB | 表示 | ![]() |
PDBx/mmJSON形式 | ![]() | ツリー表示 | ![]() | |
その他 | ![]() |
-検証レポート
文書・要旨 | ![]() | 378.4 KB | 表示 | ![]() |
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文書・詳細版 | ![]() | 401.5 KB | 表示 | |
XML形式データ | ![]() | 66.4 KB | 表示 | |
CIF形式データ | ![]() | 101.3 KB | 表示 | |
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-関連構造データ
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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 , 3種, 3分子 AEI
#1: タンパク質 | 分子量: 291321.938 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() 発現宿主: ![]() ![]() 参照: UniProt: P42345, non-specific serine/threonine protein kinase |
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#3: タンパク質 | 分子量: 192472.922 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() 発現宿主: ![]() ![]() 参照: UniProt: Q6R327 |
#5: タンパク質 | 分子量: 46365.832 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() 発現宿主: ![]() ![]() 参照: UniProt: Q8TB45 |
-Target of rapamycin complex ... , 2種, 2分子 CG
#2: タンパク質 | 分子量: 35910.090 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() 発現宿主: ![]() ![]() 参照: UniProt: Q9BVC4 |
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#4: タンパク質 | 分子量: 59206.738 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() 発現宿主: ![]() ![]() 参照: UniProt: Q9BPZ7 |
-非ポリマー , 3種, 3分子 ![](data/chem/img/IHP.gif)
![](data/chem/img/ZN.gif)
![](data/chem/img/ACE.gif)
![](data/chem/img/ZN.gif)
![](data/chem/img/ACE.gif)
#6: 化合物 | ChemComp-IHP / |
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#7: 化合物 | ChemComp-ZN / |
#8: 化合物 | ChemComp-ACE / |
-詳細
研究の焦点であるリガンドがあるか | N |
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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: mTORC2 in complex with its regulator DEPTOR / タイプ: COMPLEX / Entity ID: #1-#5 / 由来: RECOMBINANT |
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分子量 | 値: 1.24 MDa / 実験値: NO |
由来(天然) | 生物種: ![]() |
由来(組換発現) | 生物種: ![]() ![]() |
緩衝液 | pH: 7.5 |
試料 | 濃度: 1.2 mg/ml / 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: 50 e/Å2 / 検出モード: COUNTING 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 |
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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 | ||||||||||||||||||||||||
3次元再構成 | 解像度: 3.2 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 750254 / 対称性のタイプ: POINT | ||||||||||||||||||||||||
精密化 | 最高解像度: 3.2 Å / 交差検証法: NONE | ||||||||||||||||||||||||
拘束条件 |
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