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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: 7pe9 | |||||||||||||||||||||||||||
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タイトル | cryo-EM structure of DEPTOR bound to human mTOR complex 2, DEPt-bound subset local refinement | |||||||||||||||||||||||||||
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![]() | SIGNALING PROTEIN / DEPTOR / mTOR / regulator / inhibitor / mTORC2 / DEP-domain / PDZ-domain | |||||||||||||||||||||||||||
機能・相同性 | ![]() regulation of extrinsic apoptotic signaling pathway / 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 phosphatidylinositol 3-kinase/protein kinase B signal transduction / regulation of locomotor rhythm / T-helper 1 cell lineage commitment / positive regulation of pentose-phosphate shunt / positive regulation of wound healing, spreading of epidermal cells / TORC2 signaling ...regulation of extrinsic apoptotic signaling pathway / 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 phosphatidylinositol 3-kinase/protein kinase B signal transduction / regulation of locomotor rhythm / T-helper 1 cell lineage commitment / positive regulation of pentose-phosphate shunt / positive regulation of wound healing, spreading of epidermal cells / 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 / regulation of cellular response to oxidative stress / negative regulation of TORC2 signaling / calcineurin-NFAT signaling cascade / RNA polymerase III type 3 promoter sequence-specific DNA binding / positive regulation of keratinocyte migration / regulation of osteoclast differentiation / regulation of lysosome organization / MTOR signalling / cellular response to nutrient / cellular response to L-leucine / energy reserve metabolic process / Amino acids regulate mTORC1 / regulation of autophagosome assembly / Energy dependent regulation of mTOR by LKB1-AMPK / phosphatidic acid binding / TORC1 signaling / negative regulation of Ras protein signal transduction / ruffle organization / serine/threonine protein kinase complex / embryo development ending in birth or egg hatching / cellular response to methionine / phosphatidylinositol-3,4-bisphosphate binding / negative regulation of cell size / positive regulation of ubiquitin-dependent protein catabolic process / negative regulation of TOR signaling / cellular response to osmotic stress / negative regulation of protein localization to nucleus / phosphatidylinositol-3,5-bisphosphate binding / anoikis / inositol hexakisphosphate binding / cardiac muscle cell development / negative regulation of calcineurin-NFAT signaling cascade / regulation of myelination / regulation of establishment of cell polarity / positive regulation of transcription by RNA polymerase III / negative regulation of macroautophagy / Macroautophagy / lipid biosynthetic process / positive regulation of myotube differentiation / regulation of cell size / Constitutive Signaling by AKT1 E17K in Cancer / protein kinase inhibitor activity / positive regulation of actin filament polymerization / germ cell development / phosphatidylinositol-3,4,5-trisphosphate binding / TOR signaling / behavioral response to pain / mTORC1-mediated signalling / oligodendrocyte differentiation / positive regulation of oligodendrocyte differentiation / positive regulation of translational initiation / protein serine/threonine kinase inhibitor activity / CD28 dependent PI3K/Akt signaling / HSF1-dependent transactivation / positive regulation of TOR signaling / regulation of macroautophagy / enzyme-substrate adaptor activity / 'de novo' pyrimidine nucleobase biosynthetic process / response to amino acid / positive regulation of epithelial to mesenchymal transition / vascular endothelial cell response to laminar fluid shear stress / positive regulation of lipid biosynthetic process / heart morphogenesis / cellular response to nutrient levels / neuronal action potential / negative regulation of protein kinase activity / regulation of cellular response to heat / positive regulation of lamellipodium assembly / cardiac muscle contraction / T cell costimulation / phagocytic vesicle / positive regulation of stress fiber assembly / negative regulation of TORC1 signaling / positive regulation of endothelial cell proliferation / phosphatidylinositol-4,5-bisphosphate binding / cytoskeleton organization / positive regulation of autophagy / substantia nigra development / endomembrane system / negative regulation of insulin receptor signaling pathway / GTPase activator activity 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: 3.7 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. | |||||||||||||||||||||||||||
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 | 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 | ![]() | 756.2 KB | 表示 | ![]() |
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PDB形式 | ![]() | 582.4 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 | ![]() | 1.2 MB | 表示 | ![]() |
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文書・詳細版 | ![]() | 1.2 MB | 表示 | |
XML形式データ | ![]() | 96.3 KB | 表示 | |
CIF形式データ | ![]() | 152.2 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 




#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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Has protein modification | N |
-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 | ||||||||||||||||||||||||||||||
緩衝液成分 |
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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 |
試料ホルダ | 凍結剤: NITROGEN 試料ホルダーモデル: FEI TITAN KRIOS AUTOGRID HOLDER |
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: 3.7 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 132837 / 対称性のタイプ: POINT | ||||||||||||||||||||||||||||
原子モデル構築 | PDB-ID: 6ZWM Accession code: 6ZWM / Source name: PDB / タイプ: experimental model | ||||||||||||||||||||||||||||
精密化 | 最高解像度: 3.7 Å / 交差検証法: NONE | ||||||||||||||||||||||||||||
拘束条件 |
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