登録情報 データベース : EMDB / ID : EMD-11492 構造の表示 ダウンロードとリンクタイトル cryo-EM structure of human mTOR complex 2, focused on one half マップデータ 詳細 試料複合体 : human mTOR complex 2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リガンド : PHOSPHOTHIOPHOSPHORIC ACID-ADENYLATE ESTERリガンド : INOSITOL HEXAKISPHOSPHATEリガンド : ZINC IONリガンド : ACETYL GROUP 残り2件を表示 表示を減らす 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
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 / 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 ... 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 / 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 / regulation of cellular response to oxidative stress / positive regulation of transcription of nucleolar large rRNA by RNA polymerase I / TORC1 complex / calcineurin-NFAT signaling cascade / nucleus localization / cellular response to methionine / voluntary musculoskeletal movement / regulation of osteoclast differentiation / 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 / cellular response to osmotic stress / 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 / 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 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 / 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 / protein serine/threonine kinase activator activity / response to nutrient levels / negative regulation of autophagy / cellular response to amino acid stimulus / VEGFR2 mediated vascular permeability / post-embryonic development / regulation of signal transduction by p53 class mediator 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 / 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, 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 / 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 / : / FATC domain / PIK-related kinase, FAT / FAT domain / FATC / FATC domain / PIK-related kinase / FAT domain profile. / FATC domain profile. / Quinoprotein alcohol dehydrogenase-like superfamily / Phosphatidylinositol 3- and 4-kinases signature 1. / Phosphatidylinositol 3/4-kinase, conserved site / Phosphatidylinositol 3- and 4-kinases signature 2. / Phosphatidylinositol 3-/4-kinase, catalytic domain superfamily / Phosphoinositide 3-kinase, catalytic domain / Phosphatidylinositol 3- and 4-kinase / Phosphatidylinositol 3- and 4-kinases catalytic domain profile. / Phosphatidylinositol 3-/4-kinase, catalytic domain / Armadillo-like helical / Tetratricopeptide-like helical domain superfamily / PH-like domain superfamily / Armadillo-type fold / G-protein beta WD-40 repeat / 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 / 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 / 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 : 3.0 Å 詳細 データ登録者Scaiola A / Mangia F / Imseng S / Boehringer D / Ban N / Maier T 資金援助 スイス, 3件 詳細 詳細を隠すOrganization Grant number 国 Swiss National Science Foundation 179323 スイス Swiss National Science Foundation 138262 Swiss National Science Foundation 177084 スイス
引用ジャーナル : Sci Adv / 年 : 2020タイトル : The 3.2-Å resolution structure of human mTORC2.著者 : Alain Scaiola / Francesca Mangia / Stefan Imseng / Daniel Boehringer / Karolin Berneiser / Mitsugu Shimobayashi / Edward Stuttfeld / Michael N Hall / Nenad Ban / Timm Maier / 要旨 : The protein kinase mammalian target of rapamycin (mTOR) is the central regulator of cell growth. Aberrant mTOR signaling is linked to cancer, diabetes, and neurological disorders. mTOR exerts its ... The protein kinase mammalian target of rapamycin (mTOR) is the central regulator of cell growth. Aberrant mTOR signaling is linked to cancer, diabetes, and neurological disorders. mTOR exerts its functions in two distinct multiprotein complexes, mTORC1 and mTORC2. Here, we report a 3.2-Å resolution cryo-EM reconstruction of mTORC2. It reveals entangled folds of the defining Rictor and the substrate-binding SIN1 subunits, identifies the carboxyl-terminal domain of Rictor as the source of the rapamycin insensitivity of mTORC2, and resolves mechanisms for mTORC2 regulation by complex destabilization. Two previously uncharacterized small-molecule binding sites are visualized, an inositol hexakisphosphate (InsP6) pocket in mTOR and an mTORC2-specific nucleotide binding site in Rictor, which also forms a zinc finger. Structural and biochemical analyses suggest that InsP6 and nucleotide binding do not control mTORC2 activity directly but rather have roles in folding or ternary interactions. These insights provide a firm basis for studying mTORC2 signaling and for developing mTORC2-specific inhibitors. 履歴 登録 2020年7月28日 - ヘッダ(付随情報) 公開 2020年11月18日 - マップ公開 2020年11月18日 - 更新 2020年11月18日 - 現状 2020年11月18日 処理サイト : PDBe / 状態 : 公開
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