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- PDB-7pec: cryo-EM structure of DEPTOR bound to human mTOR complex 1, DEPt-b... -
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Basic information
Entry | Database: PDB / ID: 7pec | ||||||
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Title | cryo-EM structure of DEPTOR bound to human mTOR complex 1, DEPt-bound subset local refinement | ||||||
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![]() | SIGNALING PROTEIN / DEPTOR / mTOR / regulator / inhibitor / mTORC1 / DEP-domain / PDZ-domain | ||||||
Function / homology | ![]() negative regulation of TORC2 signaling / regulation of extrinsic apoptotic signaling pathway / 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 ...negative regulation of TORC2 signaling / regulation of extrinsic apoptotic signaling pathway / 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 / TFIIIC-class transcription factor complex binding / heart valve morphogenesis / 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 autophagosome assembly / calcineurin-NFAT signaling cascade / nucleus localization / TORC1 signaling / voluntary musculoskeletal movement / positive regulation of odontoblast differentiation / 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 / phosphatidic acid binding / Energy dependent regulation of mTOR by LKB1-AMPK / negative regulation of cell size / ruffle organization / protein serine/threonine kinase inhibitor activity / positive regulation of osteoclast differentiation / cellular response to osmotic stress / enzyme-substrate adaptor activity / negative regulation of protein localization to nucleus / anoikis / cardiac muscle cell development / negative regulation of TOR signaling / 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 / protein kinase activator activity / behavioral response to pain / oligodendrocyte differentiation / Constitutive Signaling by AKT1 E17K in Cancer / mTORC1-mediated signalling / germ cell development / CD28 dependent PI3K/Akt signaling / cellular response to nutrient levels / positive regulation of phosphoprotein phosphatase activity / social behavior / HSF1-dependent transactivation / positive regulation of TOR signaling / TOR signaling / neuronal action potential / positive regulation of translational initiation / response to amino acid / positive regulation of G1/S transition of mitotic cell cycle / regulation of macroautophagy / endomembrane system / 'de novo' pyrimidine nucleobase biosynthetic process / positive regulation of autophagy / positive regulation of lamellipodium assembly / positive regulation of epithelial to mesenchymal transition / 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 / 14-3-3 protein binding / positive regulation of endothelial cell proliferation / cytoskeleton organization / T cell costimulation / cellular response to amino acid starvation / phagocytic vesicle / positive regulation of glycolytic process / cellular response to starvation / negative regulation of autophagy / protein serine/threonine kinase activator activity / response to nutrient levels / response to nutrient / post-embryonic development / VEGFR2 mediated vascular permeability / positive regulation of peptidyl-threonine phosphorylation / regulation of signal transduction by p53 class mediator / Regulation of PTEN gene transcription Similarity search - Function | ||||||
Biological species | ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 4.24 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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PDBx/mmCIF format | ![]() | 702.2 KB | Display | ![]() |
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PDB format | ![]() | 560.2 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 1 MB | Display | ![]() |
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Full document | ![]() | 1.1 MB | Display | |
Data in XML | ![]() | 95 KB | Display | |
Data in CIF | ![]() | 145.8 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 13352MC ![]() 7pe7C ![]() 7pe8C ![]() 7pe9C ![]() 7peaC ![]() 7pebC ![]() 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
#1: Protein | Mass: 287484.156 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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#2: Protein | Mass: 35910.090 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
#3: Protein | Mass: 155963.094 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
#4: Protein | Mass: 46365.832 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
#5: Chemical | ChemComp-IHP / |
Has ligand of interest | N |
-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: mTORC1 in complex with its regulator DEPTOR / Type: COMPLEX / Entity ID: #1-#4 / Source: RECOMBINANT | ||||||||||||||||||||||||||||||
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Molecular weight | Value: 1.04 MDa / Experimental value: NO | ||||||||||||||||||||||||||||||
Source (natural) | Organism: ![]() | ||||||||||||||||||||||||||||||
Source (recombinant) | Organism: ![]() ![]() | ||||||||||||||||||||||||||||||
Buffer solution | pH: 7.5 | ||||||||||||||||||||||||||||||
Buffer component |
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Specimen | Conc.: 1.4 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
Microscopy | Model: TFS GLACIOS |
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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 K3 (6k x 4k) |
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Processing
Software | Name: PHENIX / Version: 1.19_4092: / Classification: refinement | ||||||||||||||||||||||||||||
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EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||
3D reconstruction | Resolution: 4.24 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 211021 / Symmetry type: POINT | ||||||||||||||||||||||||||||
Atomic model building | PDB-ID: 6BCX Accession code: 6BCX / Source name: PDB / Type: experimental model | ||||||||||||||||||||||||||||
Refine LS restraints |
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