- EMDB-13097: human DEPTOR in a complex with mutant human mTORC1 A1459P -
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基本情報
登録情報
データベース: EMDB / ID: EMD-13097
タイトル
human DEPTOR in a complex with mutant human mTORC1 A1459P
マップデータ
mTORC1 with mTOR A1459P mutant in a complex with DEPTOR
試料
複合体: COMPLEX OF HUMAN MUTANT MTORC1 A1459P WITH THE INHIBITORY PROTEIN DEPTOR
複合体: mTORC1 with mutant A1459P mTOR
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: Regulatory-associated protein of mTOR
複合体: DEPTOR
タンパク質・ペプチド: DEP domain-containing mTOR-interacting protein
キーワード
kinase / PIKK / mTOR / cancer-associated mutation / DEPTOR / partial inhibitor / cancer / PDZ / non-canonical PDZ binding / SIGNALING PROTEIN
機能・相同性
機能・相同性情報
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 / 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 / TORC2 signaling / TORC2 complex ...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 / 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 / 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 / positive regulation of transcription of nucleolar large rRNA by RNA polymerase I / negative regulation of TORC2 signaling / calcineurin-NFAT signaling cascade / voluntary musculoskeletal movement / positive regulation of odontoblast differentiation / regulation of osteoclast differentiation / RNA polymerase III type 3 promoter sequence-specific DNA binding / positive regulation of keratinocyte migration / regulation of lysosome organization / phosphatidic acid binding / Amino acids regulate mTORC1 / cellular response to L-leucine / MTOR signalling / cellular response to nutrient / regulation of autophagosome assembly / Energy dependent regulation of mTOR by LKB1-AMPK / TORC1 signaling / energy reserve metabolic process / ruffle organization / serine/threonine protein kinase complex / negative regulation of cell size / cellular response to methionine / positive regulation of osteoclast differentiation / positive regulation of ubiquitin-dependent protein catabolic process / inositol hexakisphosphate binding / cellular response to osmotic stress / negative regulation of TOR signaling / anoikis / protein serine/threonine kinase inhibitor activity / negative regulation of protein localization to nucleus / cardiac muscle cell development / negative regulation of calcineurin-NFAT signaling cascade / regulation of myelination / positive regulation of transcription by RNA polymerase III / positive regulation of peptidyl-threonine phosphorylation / positive regulation of actin filament polymerization / negative regulation of macroautophagy / Macroautophagy / regulation of cell size / positive regulation of myotube differentiation / protein kinase inhibitor activity / Constitutive Signaling by AKT1 E17K in Cancer / social behavior / oligodendrocyte differentiation / germ cell development / behavioral response to pain / TOR signaling / mTORC1-mediated signalling / positive regulation of oligodendrocyte differentiation / positive regulation of translational initiation / protein kinase activator activity / CD28 dependent PI3K/Akt signaling / positive regulation of TOR signaling / response to amino acid / HSF1-dependent transactivation / regulation of macroautophagy / positive regulation of G1/S transition of mitotic cell cycle / enzyme-substrate adaptor activity / 'de novo' pyrimidine nucleobase biosynthetic process / cellular response to nutrient levels / vascular endothelial cell response to laminar fluid shear stress / neuronal action potential / positive regulation of lipid biosynthetic process / positive regulation of epithelial to mesenchymal transition / heart morphogenesis / regulation of cellular response to heat / positive regulation of lamellipodium assembly / cardiac muscle contraction / positive regulation of peptidyl-serine phosphorylation / phagocytic vesicle / positive regulation of stress fiber assembly / positive regulation of autophagy / negative regulation of TORC1 signaling / positive regulation of endothelial cell proliferation / 14-3-3 protein binding / T cell costimulation / cytoskeleton organization / endomembrane system / negative regulation of autophagy / cellular response to amino acid starvation / GTPase activator activity / protein serine/threonine kinase activator activity / guanyl-nucleotide exchange factor activity / positive regulation of glycolytic process 類似検索 - 分子機能
DEP domain-containing mTOR-interacting protein, DEP domain 1 / DEP domain-containing mTOR-interacting protein, DEP domain 2 / Raptor, N-terminal CASPase-like domain / Raptor N-terminal CASPase like domain / Raptor N-terminal CASPase like domain / Regulatory associated protein of TOR / Target of rapamycin complex subunit LST8 / : / Domain of unknown function DUF3385, target of rapamycin protein / Serine/threonine-protein kinase mTOR domain ...DEP domain-containing mTOR-interacting protein, DEP domain 1 / DEP domain-containing mTOR-interacting protein, DEP domain 2 / Raptor, N-terminal CASPase-like domain / Raptor N-terminal CASPase like domain / Raptor N-terminal CASPase like domain / Regulatory associated protein of TOR / 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 / Serine/threonine-protein kinase ATR-like, HEAT repeats / HEAT repeat / HEAT repeat / Domain found in Dishevelled, Egl-10, and Pleckstrin (DEP) / DEP domain profile. / Domain found in Dishevelled, Egl-10, and Pleckstrin / DEP 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 / 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 / Armadillo-type fold / G-protein beta WD-40 repeat / Winged helix DNA-binding domain superfamily / WD40 repeat, conserved site / Trp-Asp (WD) repeats signature. / WD domain, G-beta repeat / Trp-Asp (WD) repeats profile. / Trp-Asp (WD) repeats circular profile. / WD40 repeats / WD40 repeat / WD40-repeat-containing domain superfamily / 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 / Regulatory-associated protein of mTOR / DEP domain-containing mTOR-interacting protein / Target of rapamycin complex subunit LST8 類似検索 - 構成要素
ジャーナル: Elife / 年: 2021 タイトル: Bipartite binding and partial inhibition links DEPTOR and mTOR in a mutually antagonistic embrace. 著者: Maren Heimhalt / Alex Berndt / Jane Wagstaff / Madhanagopal Anandapadamanaban / Olga Perisic / Sarah Maslen / Stephen McLaughlin / Conny Wing-Heng Yu / Glenn R Masson / Andreas Boland / ...著者: Maren Heimhalt / Alex Berndt / Jane Wagstaff / Madhanagopal Anandapadamanaban / Olga Perisic / Sarah Maslen / Stephen McLaughlin / Conny Wing-Heng Yu / Glenn R Masson / Andreas Boland / Xiaodan Ni / Keitaro Yamashita / Garib N Murshudov / Mark Skehel / Stefan M Freund / Roger L Williams / 要旨: The mTORC1 kinase complex regulates cell growth, proliferation, and survival. Because mis-regulation of DEPTOR, an endogenous mTORC1 inhibitor, is associated with some cancers, we reconstituted ...The mTORC1 kinase complex regulates cell growth, proliferation, and survival. Because mis-regulation of DEPTOR, an endogenous mTORC1 inhibitor, is associated with some cancers, we reconstituted mTORC1 with DEPTOR to understand its function. We find that DEPTOR is a unique mTORC1 inhibitor that may have evolved to preserve feedback inhibition of PI3K. Counterintuitively, mTORC1 activated by RHEB or oncogenic mutation is much more potently inhibited by DEPTOR. Although DEPTOR partially inhibits mTORC1, mTORC1 prevents this inhibition by phosphorylating DEPTOR, a mutual antagonism that requires no exogenous factors. Structural analyses of the mTORC1/DEPTOR complex showed DEPTOR's PDZ domain interacting with the mTOR FAT region, and the unstructured linker preceding the PDZ binding to the mTOR FRB domain. The linker and PDZ form the minimal inhibitory unit, but the N-terminal tandem DEP domains also significantly contribute to inhibition.
全体 : COMPLEX OF HUMAN MUTANT MTORC1 A1459P WITH THE INHIBITORY PROTEIN...
全体
名称: COMPLEX OF HUMAN MUTANT MTORC1 A1459P WITH THE INHIBITORY PROTEIN DEPTOR
要素
複合体: COMPLEX OF HUMAN MUTANT MTORC1 A1459P WITH THE INHIBITORY PROTEIN DEPTOR
複合体: mTORC1 with mutant A1459P mTOR
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: Regulatory-associated protein of mTOR
複合体: DEPTOR
タンパク質・ペプチド: DEP domain-containing mTOR-interacting protein
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超分子 #1: COMPLEX OF HUMAN MUTANT MTORC1 A1459P WITH THE INHIBITORY PROTEIN...
超分子
名称: COMPLEX OF HUMAN MUTANT MTORC1 A1459P WITH THE INHIBITORY PROTEIN DEPTOR タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: all 詳細: An mTORC1 complex bound to two copies of DEPTOR. Each mTORC1 complex consists of a dimer of an mTOR/LST8/RAPTOR heterotrimer. The mTOR is an A1459P mutant.