+データを開く
-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 | ||||||
要素 |
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キーワード | SIGNALING PROTEIN / DEPTOR / mTOR / regulator / inhibitor / mTORC2 / DEP-domain / PDZ-domain | ||||||
機能・相同性 | 機能・相同性情報 negative regulation of TORC2 signaling / regulation of extrinsic apoptotic signaling pathway / TORC2 signaling / regulation of peptidyl-serine phosphorylation / 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 / T-helper 1 cell lineage commitment / positive regulation of pentose-phosphate shunt / regulation of locomotor rhythm ...negative regulation of TORC2 signaling / regulation of extrinsic apoptotic signaling pathway / TORC2 signaling / regulation of peptidyl-serine phosphorylation / 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 / T-helper 1 cell lineage commitment / positive regulation of pentose-phosphate shunt / 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 / regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / regulation of membrane permeability / heart valve morphogenesis / negative regulation of lysosome organization / RNA polymerase III type 3 promoter sequence-specific DNA binding / positive regulation of transcription of nucleolar large rRNA by RNA polymerase I / regulation of cellular response to oxidative stress / TORC1 complex / calcineurin-NFAT signaling cascade / nucleus localization / cellular response to methionine / regulation of osteoclast differentiation / voluntary musculoskeletal movement / TORC1 signaling / positive regulation of keratinocyte migration / cellular response to L-leucine / MTOR signalling / Amino acids regulate mTORC1 / cellular response to nutrient / phosphatidic acid binding / regulation of autophagosome assembly / Energy dependent regulation of mTOR by LKB1-AMPK / energy reserve metabolic process / negative regulation of cell size / ruffle organization / phosphatidylinositol-3,4-bisphosphate binding / negative regulation of Ras protein signal transduction / protein serine/threonine kinase inhibitor activity / cellular response to osmotic stress / negative regulation of TOR signaling / negative regulation of protein localization to nucleus / anoikis / cardiac muscle cell development / 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 / negative regulation of macroautophagy / regulation of cell size / positive regulation of oligodendrocyte differentiation / Macroautophagy / positive regulation of actin filament polymerization / lysosome organization / positive regulation of myotube differentiation / protein kinase inhibitor activity / oligodendrocyte differentiation / behavioral response to pain / Constitutive Signaling by AKT1 E17K in Cancer / germ cell development / mTORC1-mediated signalling / CD28 dependent PI3K/Akt signaling / phosphatidylinositol-3,4,5-trisphosphate binding / : / HSF1-dependent transactivation / neuronal action potential / TOR signaling / positive regulation of TOR signaling / response to amino acid / endomembrane system / cellular response to nutrient levels / positive regulation of translational initiation / regulation of macroautophagy / '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 / response to nutrient / cardiac muscle contraction / regulation of cellular response to heat / phagocytic vesicle / positive regulation of stress fiber assembly / negative regulation of TORC1 signaling / cytoskeleton organization / Regulation of PTEN gene transcription / positive regulation of endothelial cell proliferation / T cell costimulation / phosphatidylinositol-4,5-bisphosphate binding / substantia nigra development / cellular response to starvation / phosphorylation / positive regulation of glycolytic process / cellular response to amino acid starvation 類似検索 - 分子機能 | ||||||
生物種 | Homo sapiens (ヒト) | ||||||
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 | ||||||
データ登録者 | Waelchli, M. / Maier, T. | ||||||
資金援助 | スイス, 1件
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引用 | ジャーナル: Elife / 年: 2021 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 |
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 | 7pe9.cif.gz | 750.1 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb7pe9.ent.gz | 592.7 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 7pe9.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/pe/7pe9 ftp://data.pdbj.org/pub/pdb/validation_reports/pe/7pe9 | 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
-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) Homo sapiens (ヒト) / 遺伝子: MTOR, FRAP, FRAP1, FRAP2, RAFT1, RAPT1 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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#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) Homo sapiens (ヒト) / 遺伝子: RICTOR, KIAA1999 発現宿主: Spodoptera frugiperda (ツマジロクサヨトウ) 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) Homo sapiens (ヒト) / 遺伝子: DEPTOR, DEPDC6 発現宿主: Spodoptera frugiperda (ツマジロクサヨトウ) 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) Homo sapiens (ヒト) / 遺伝子: MLST8, GBL, LST8 発現宿主: Spodoptera frugiperda (ツマジロクサヨトウ) 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) Homo sapiens (ヒト) / 遺伝子: MAPKAP1, MIP1, SIN1 発現宿主: Spodoptera frugiperda (ツマジロクサヨトウ) 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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-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: 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: Homo sapiens (ヒト) | ||||||||||||||||||||||||||||||
由来(組換発現) | 生物種: Spodoptera frugiperda (ツマジロクサヨトウ) | ||||||||||||||||||||||||||||||
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 |
-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: 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 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) |
-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 | ||||||||||||||||||||||||||||
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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