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- PDB-7pe9: cryo-EM structure of DEPTOR bound to human mTOR complex 2, DEPt-b... -
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Basic information
Entry | Database: PDB / ID: 7pe9 | ||||||
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Title | cryo-EM structure of DEPTOR bound to human mTOR complex 2, DEPt-bound subset local refinement | ||||||
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![]() | SIGNALING PROTEIN / DEPTOR / mTOR / regulator / inhibitor / mTORC2 / DEP-domain / PDZ-domain | ||||||
Function / homology | ![]() negative regulation of TORC2 signaling / regulation of extrinsic apoptotic signaling pathway / TORC2 signaling / regulation of peptidyl-serine phosphorylation / positive regulation of cytoplasmic translational initiation / positive regulation of pentose-phosphate shunt / RNA polymerase III type 1 promoter sequence-specific DNA binding / RNA polymerase III type 2 promoter sequence-specific DNA binding / 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 / positive regulation of cytoplasmic translational initiation / positive regulation of pentose-phosphate shunt / RNA polymerase III type 1 promoter sequence-specific DNA binding / RNA polymerase III type 2 promoter sequence-specific DNA binding / T-helper 1 cell lineage commitment / regulation of locomotor rhythm / positive regulation of wound healing, spreading of epidermal cells / cellular response to leucine starvation / 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 / TORC2 complex / TORC1 complex / positive regulation of transcription of nucleolar large rRNA by RNA polymerase I / regulation of cellular response to oxidative stress / regulation of autophagosome assembly / calcineurin-NFAT signaling cascade / 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 / negative regulation of cell size / ruffle organization / protein serine/threonine kinase inhibitor activity / 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 / negative regulation of TOR signaling / 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 / regulation of cell size / Macroautophagy / positive regulation of oligodendrocyte differentiation / negative regulation of macroautophagy / positive regulation of actin filament polymerization / lysosome organization / positive regulation of myotube differentiation / protein kinase inhibitor activity / 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 / cellular response to nutrient levels / positive regulation of phosphoprotein phosphatase activity / phosphatidylinositol-3,4,5-trisphosphate binding / HSF1-dependent transactivation / TOR signaling / positive regulation of TOR signaling / neuronal action potential / positive regulation of translational initiation / response to amino acid / regulation of macroautophagy / endomembrane system / 'de novo' pyrimidine nucleobase biosynthetic process / positive regulation of autophagy / positive regulation of epithelial to mesenchymal transition / positive regulation of lamellipodium assembly / positive regulation of lipid biosynthetic process / heart morphogenesis / cardiac muscle contraction / regulation of cellular response to heat / 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 / phosphatidylinositol-4,5-bisphosphate binding / cellular response to amino acid starvation / positive regulation of glycolytic process / cellular response to starvation / phagocytic vesicle / negative regulation of autophagy / protein serine/threonine kinase activator activity / response to nutrient levels / response to nutrient Similarity search - Function | ||||||
Biological species | ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.7 Å | ||||||
![]() | Waelchli, M. / Maier, T. | ||||||
Funding support | ![]()
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![]() | ![]() 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
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Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 750.1 KB | Display | ![]() |
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PDB format | ![]() | 592.7 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 381.4 KB | Display | ![]() |
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Full document | ![]() | 413.3 KB | Display | |
Data in XML | ![]() | 71.9 KB | Display | |
Data in CIF | ![]() | 109.9 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 13349MC ![]() 7pe7C ![]() 7pe8C ![]() 7peaC ![]() 7pebC ![]() 7pecC ![]() 7pedC M: map data used to model this data C: citing same article ( |
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Similar structure data |
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Links
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Assembly
Deposited unit | ![]()
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Components
-Protein , 3 types, 3 molecules AEI
#1: Protein | Mass: 291321.938 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() References: UniProt: P42345, non-specific serine/threonine protein kinase |
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#3: Protein | Mass: 192472.922 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
#5: Protein | Mass: 46365.832 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
-Target of rapamycin complex ... , 2 types, 2 molecules CG
#2: Protein | Mass: 35910.090 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
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#4: Protein | Mass: 59206.738 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
-Non-polymers , 3 types, 3 molecules ![](data/chem/img/IHP.gif)
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#6: Chemical | ChemComp-IHP / |
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#7: Chemical | ChemComp-ZN / |
#8: Chemical | ChemComp-ACE / |
-Details
Has ligand of interest | N |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
Component | Name: mTORC2 in complex with its regulator DEPTOR / Type: COMPLEX / Entity ID: #1-#5 / Source: RECOMBINANT | ||||||||||||||||||||||||||||||
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Molecular weight | Value: 1.24 MDa / Experimental value: NO | ||||||||||||||||||||||||||||||
Source (natural) | Organism: ![]() | ||||||||||||||||||||||||||||||
Source (recombinant) | Organism: ![]() ![]() | ||||||||||||||||||||||||||||||
Buffer solution | pH: 7.5 | ||||||||||||||||||||||||||||||
Buffer component |
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Specimen | Conc.: 1.2 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||||||||||||
Vitrification | Cryogen name: ETHANE |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD |
Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Electron dose: 50 e/Å2 / Detector mode: COUNTING / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
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Processing
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EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||
3D reconstruction | Resolution: 3.7 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 132837 / Symmetry type: POINT | ||||||||||||||||||||||||||||
Atomic model building | PDB-ID: 6ZWM | ||||||||||||||||||||||||||||
Refinement | Highest resolution: 3.7 Å / Cross valid method: NONE | ||||||||||||||||||||||||||||
Refine LS restraints |
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