登録情報 データベース : EMDB / ID : EMD-13348 構造の表示 ダウンロードとリンクタイトル cryo-EM structure of DEPTOR bound to human mTOR complex 2, focussed on one protomer マップデータ 詳細 試料複合体 : mTORC2 in complex with its regulator DEPTORタンパク質・ペプチド : Serine/threonine-protein kinase mTORタンパク質・ペプチド : Target of rapamycin complex subunit LST8タンパク質・ペプチド : Rapamycin-insensitive companion of mTORタンパク質・ペプチド : Target of rapamycin complex 2 subunit MAPKAP1タンパク質・ペプチド : DEP domain-containing mTOR-interacting proteinリガンド : INOSITOL HEXAKISPHOSPHATEリガンド : ZINC IONリガンド : ACETYL GROUP 詳細機能・相同性 機能・相同性情報分子機能 ドメイン・相同性 構成要素
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 / 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 ... 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 / 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 / positive regulation of wound healing, spreading of epidermal cells / TORC2 complex / cellular response to leucine starvation / TFIIIC-class transcription factor complex binding / regulation of membrane permeability / negative regulation of lysosome organization / heart valve morphogenesis / nucleus localization / RNA polymerase III type 3 promoter sequence-specific DNA binding / TORC1 complex / positive regulation of transcription of nucleolar large rRNA by RNA polymerase I / regulation of cellular response to oxidative stress / calcineurin-NFAT signaling cascade / voluntary musculoskeletal movement / TORC1 signaling / regulation of osteoclast differentiation / positive regulation of keratinocyte migration / phosphatidic acid binding / cellular response to L-leucine / Amino acids regulate mTORC1 / MTOR signalling / cellular response to nutrient / regulation of autophagosome assembly / cellular response to methionine / Energy dependent regulation of mTOR by LKB1-AMPK / energy reserve metabolic process / negative regulation of cell size / ruffle organization / negative regulation of Ras protein signal transduction / phosphatidylinositol-3,4-bisphosphate binding / cellular response to osmotic stress / protein serine/threonine kinase inhibitor activity / negative regulation of TOR signaling / phosphatidylinositol-3,5-bisphosphate binding / negative regulation of protein localization to nucleus / anoikis / cardiac muscle cell development / embryo development ending in birth or egg hatching / regulation of establishment of cell polarity / positive regulation of transcription by RNA polymerase III / negative regulation of calcineurin-NFAT signaling cascade / regulation of myelination / positive regulation of actin filament polymerization / regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / regulation of cell size / negative regulation of macroautophagy / positive regulation of oligodendrocyte differentiation / lysosome organization / Macroautophagy / positive regulation of myotube differentiation / behavioral response to pain / protein kinase inhibitor activity / oligodendrocyte differentiation / Constitutive Signaling by AKT1 E17K in Cancer / mTORC1-mediated signalling / germ cell development / phosphatidylinositol-3,4,5-trisphosphate binding / : / CD28 dependent PI3K/Akt signaling / HSF1-dependent transactivation / neuronal action potential / positive regulation of TOR signaling / response to amino acid / TOR signaling / endomembrane system / 'de novo' pyrimidine nucleobase biosynthetic process / regulation of macroautophagy / positive regulation of translational initiation / cellular response to nutrient levels / positive regulation of lamellipodium assembly / phagocytic vesicle / positive regulation of autophagy / heart morphogenesis / positive regulation of lipid biosynthetic process / positive regulation of epithelial to mesenchymal transition / phosphorylation / cardiac muscle contraction / regulation of cellular response to heat / phosphatidylinositol-4,5-bisphosphate binding / positive regulation of stress fiber assembly / negative regulation of TORC1 signaling / cytoskeleton organization / positive regulation of endothelial cell proliferation / T cell costimulation / substantia nigra development / cellular response to amino acid starvation / cellular response to starvation / post-embryonic development / positive regulation of glycolytic process / negative regulation of autophagy 類似検索 - 分子機能 Rapamycin-insensitive companion of mTOR, N-terminal domain / Pianissimo family / Rapamycin-insensitive companion of mTOR, phosphorylation-site / Rapamycin-insensitive companion of mTOR, middle domain / Rapamycin-insensitive companion of mTOR, domain 5 / Rapamycin-insensitive companion of mTOR, domain 4 / DEP domain-containing mTOR-interacting protein, DEP domain 1 / DEP domain-containing mTOR-interacting protein, DEP domain 2 / Rapamycin-insensitive companion of mTOR RasGEF_N domain / Rapamycin-insensitive companion of mTOR, N-term ... Rapamycin-insensitive companion of mTOR, N-terminal domain / Pianissimo family / Rapamycin-insensitive companion of mTOR, phosphorylation-site / Rapamycin-insensitive companion of mTOR, middle domain / Rapamycin-insensitive companion of mTOR, domain 5 / Rapamycin-insensitive companion of mTOR, domain 4 / DEP domain-containing mTOR-interacting protein, DEP domain 1 / DEP domain-containing mTOR-interacting protein, DEP domain 2 / Rapamycin-insensitive companion of mTOR RasGEF_N domain / Rapamycin-insensitive companion of mTOR, N-term / Rapamycin-insensitive companion of mTOR, phosphorylation-site / Rapamycin-insensitive companion of mTOR, middle domain / Rapamycin-insensitive companion of mTOR, domain 5 / Rapamycin-insensitive companion of mTOR RasGEF_N domain / Rapamycin-insensitive companion of mTOR, middle domain / Rapamycin-insensitive companion of mTOR, N-term / Rapamycin-insensitive companion of mTOR, phosphorylation-site / Rapamycin-insensitive companion of mTOR, domain 5 / Sin1, N-terminal / Stress-activated map kinase interacting protein 1 (SIN1) / TORC2 component Sin1/Avo1 / SAPK-interacting protein 1, Pleckstrin-homology domain / Sin1, middle CRIM domain / SAPK-interacting protein 1 (Sin1), middle CRIM domain / SAPK-interacting protein 1 (Sin1), Pleckstrin-homology / : / Target of rapamycin complex subunit LST8 / Domain of unknown function DUF3385, target of rapamycin protein / Serine/threonine-protein kinase mTOR domain / Domain of unknown function / FKBP12-rapamycin binding domain / Serine/threonine-protein kinase TOR / FKBP12-rapamycin binding domain superfamily / FKBP12-rapamycin binding domain / Rapamycin binding domain / Domain found in Dishevelled, Egl-10, and Pleckstrin (DEP) / DEP domain profile. / Domain found in Dishevelled, Egl-10, and Pleckstrin / DEP domain / : / PIK-related kinase, FAT / FAT domain / FATC domain / FAT domain profile. / FATC domain profile. / FATC / FATC domain / PIK-related kinase / Quinoprotein alcohol dehydrogenase-like superfamily / Phosphatidylinositol 3- and 4-kinases signature 1. / Phosphatidylinositol 3- and 4-kinases signature 2. / Phosphatidylinositol 3/4-kinase, conserved site / Phosphatidylinositol 3-/4-kinase, catalytic domain superfamily / Phosphoinositide 3-kinase, catalytic domain / Phosphatidylinositol 3- and 4-kinases catalytic domain profile. / Phosphatidylinositol 3-/4-kinase, catalytic domain / Phosphatidylinositol 3- and 4-kinase / PDZ domain profile. / Domain present in PSD-95, Dlg, and ZO-1/2. / PDZ domain / PDZ superfamily / Armadillo-like helical / Tetratricopeptide-like helical domain superfamily / PH-like domain superfamily / Armadillo-type fold / G-protein beta WD-40 repeat / Winged helix DNA-binding domain superfamily / WD40 repeat, conserved site / Trp-Asp (WD) repeats signature. / Trp-Asp (WD) repeats profile. / Trp-Asp (WD) repeats circular profile. / WD domain, G-beta repeat / WD40 repeats / WD40 repeat / Winged helix-like DNA-binding domain superfamily / WD40/YVTN repeat-like-containing domain superfamily / Protein kinase-like domain superfamily 類似検索 - ドメイン・相同性 Serine/threonine-protein kinase mTOR / Rapamycin-insensitive companion of mTOR / DEP domain-containing mTOR-interacting protein / Target of rapamycin complex 2 subunit MAPKAP1 / Target of rapamycin complex subunit LST8 類似検索 - 構成要素生物種 Homo sapiens (ヒト)手法 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度 : 3.2 Å 詳細 データ登録者Waelchli M / Maier T 資金援助 スイス, 1件 詳細 詳細を隠すOrganization Grant number 国 Swiss National Science Foundation 179323 スイス
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 登録 2021年8月9日 - ヘッダ(付随情報) 公開 2021年9月8日 - マップ公開 2021年9月8日 - 更新 2021年9月29日 - 現状 2021年9月29日 処理サイト : PDBe / 状態 : 公開
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