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Yorodumi- PDB-7pe7: cryo-EM structure of DEPTOR bound to human mTOR complex 2, overal... -
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-Basic information
Entry | Database: PDB / ID: 7pe7 | ||||||
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Title | cryo-EM structure of DEPTOR bound to human mTOR complex 2, overall refinement | ||||||
Components |
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Keywords | SIGNALING PROTEIN / DEPTOR / mTOR / regulator / inhibitor / mTORC2 / DEP-domain / PDZ-domain | ||||||
Function / homology | Function and homology information 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 / positive regulation of pentose-phosphate shunt / T-helper 1 cell lineage commitment / 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 / positive regulation of pentose-phosphate shunt / T-helper 1 cell lineage commitment / regulation of locomotor rhythm / positive regulation of wound healing, spreading of epidermal cells / cellular response to leucine starvation / TORC2 complex / regulation of membrane permeability / heart valve morphogenesis / TFIIIC-class transcription factor complex binding / negative regulation of lysosome organization / 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 / regulation of autophagosome assembly / nucleus localization / TORC1 signaling / voluntary musculoskeletal movement / regulation of osteoclast differentiation / positive regulation of keratinocyte migration / cellular response to L-leucine / MTOR signalling / Amino acids regulate mTORC1 / cellular response to nutrient / energy reserve metabolic process / Energy dependent regulation of mTOR by LKB1-AMPK / phosphatidic acid binding / ruffle organization / protein serine/threonine kinase inhibitor activity / negative regulation of cell size / phosphatidylinositol-3,4-bisphosphate binding / negative regulation of Ras protein signal transduction / cellular response to osmotic stress / anoikis / phosphatidylinositol-3,5-bisphosphate binding / negative regulation of protein localization to nucleus / cardiac muscle cell development / negative regulation of TOR signaling / 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 / regulation of cell size / negative regulation of macroautophagy / Macroautophagy / positive regulation of oligodendrocyte differentiation / lysosome organization / positive regulation of actin filament polymerization / protein kinase inhibitor activity / positive regulation of myotube differentiation / behavioral response to pain / regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / oligodendrocyte differentiation / mTORC1-mediated signalling / Constitutive Signaling by AKT1 E17K in Cancer / germ cell development / CD28 dependent PI3K/Akt signaling / phosphatidylinositol-3,4,5-trisphosphate binding / positive regulation of phosphoprotein phosphatase activity / cellular response to nutrient levels / HSF1-dependent transactivation / TOR signaling / positive regulation of TOR signaling / neuronal action potential / regulation of macroautophagy / positive regulation of translational initiation / endomembrane system / response to amino acid / 'de novo' pyrimidine nucleobase biosynthetic process / positive regulation of lamellipodium assembly / positive regulation of autophagy / positive regulation of epithelial to mesenchymal transition / positive regulation of lipid biosynthetic process / regulation of cellular response to heat / heart morphogenesis / cardiac muscle contraction / phagocytic vesicle / positive regulation of stress fiber assembly / negative regulation of TORC1 signaling / positive regulation of endothelial cell proliferation / cytoskeleton organization / T cell costimulation / phosphatidylinositol-4,5-bisphosphate binding / substantia nigra development / cellular response to amino acid starvation / cellular response to starvation / positive regulation of glycolytic process / protein serine/threonine kinase activator activity / response to nutrient levels / negative regulation of autophagy / response to nutrient Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.41 Å | ||||||
Authors | Waelchli, M. / Maier, T. | ||||||
Funding support | Switzerland, 1items
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Citation | Journal: Elife / Year: 2021 Title: Regulation of human mTOR complexes by DEPTOR. Authors: Matthias Wälchli / Karolin Berneiser / Francesca Mangia / Stefan Imseng / Louise-Marie Craigie / Edward Stuttfeld / Michael N Hall / Timm Maier / Abstract: 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. | ||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 7pe7.cif.gz | 1.3 MB | Display | PDBx/mmCIF format |
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PDB format | pdb7pe7.ent.gz | 1.1 MB | Display | PDB format |
PDBx/mmJSON format | 7pe7.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/pe/7pe7 ftp://data.pdbj.org/pub/pdb/validation_reports/pe/7pe7 | HTTPS FTP |
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-Related structure data
Related structure data | 13347MC 7pe8C 7pe9C 7peaC 7pebC 7pecC 7pedC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data |
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-Assembly
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Noncrystallographic symmetry (NCS) | NCS domain:
NCS domain segments:
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