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Yorodumi- PDB-7peb: cryo-EM structure of DEPTOR bound to human mTOR complex 1, focuss... -
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-Basic information
Entry | Database: PDB / ID: 7peb | ||||||
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Title | cryo-EM structure of DEPTOR bound to human mTOR complex 1, focussed on one protomer | ||||||
Components |
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Keywords | SIGNALING PROTEIN / DEPTOR / mTOR / regulator / inhibitor / mTORC1 / DEP-domain / PDZ-domain | ||||||
Function / homology | Function and homology information negative regulation of TORC2 signaling / regulation of extrinsic apoptotic signaling pathway / 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 ...negative regulation of TORC2 signaling / regulation of extrinsic apoptotic signaling pathway / 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 / TFIIIC-class transcription factor complex binding / TORC2 complex / heart valve morphogenesis / regulation of membrane permeability / 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 / calcineurin-NFAT signaling cascade / regulation of autophagosome assembly / TORC1 signaling / positive regulation of odontoblast differentiation / 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 / nucleus localization / negative regulation of TOR signaling / ruffle organization / protein serine/threonine kinase inhibitor activity / negative regulation of cell size / cellular response to osmotic stress / positive regulation of osteoclast differentiation / enzyme-substrate adaptor activity / anoikis / cardiac muscle cell development / positive regulation of transcription by RNA polymerase III / negative regulation of protein localization to nucleus / regulation of myelination / negative regulation of calcineurin-NFAT signaling cascade / Macroautophagy / regulation of cell size / negative regulation of macroautophagy / lysosome organization / positive regulation of oligodendrocyte differentiation / positive regulation of actin filament polymerization / protein kinase activator activity / protein kinase inhibitor activity / positive regulation of myotube differentiation / behavioral response to pain / TOR signaling / oligodendrocyte differentiation / mTORC1-mediated signalling / germ cell development / Constitutive Signaling by AKT1 E17K in Cancer / social behavior / cellular response to nutrient levels / CD28 dependent PI3K/Akt signaling / positive regulation of phosphoprotein phosphatase activity / positive regulation of translational initiation / neuronal action potential / HSF1-dependent transactivation / positive regulation of TOR signaling / positive regulation of G1/S transition of mitotic cell cycle / positive regulation of epithelial to mesenchymal transition / regulation of macroautophagy / endomembrane system / 'de novo' pyrimidine nucleobase biosynthetic process / response to amino acid / positive regulation of lipid biosynthetic process / phagocytic vesicle / positive regulation of lamellipodium assembly / positive regulation of autophagy / heart morphogenesis / regulation of cellular response to heat / cytoskeleton organization / cardiac muscle contraction / negative regulation of TORC1 signaling / positive regulation of stress fiber assembly / cellular response to amino acid starvation / T cell costimulation / cellular response to starvation / positive regulation of endothelial cell proliferation / positive regulation of glycolytic process / protein serine/threonine kinase activator activity / response to nutrient levels / post-embryonic development / response to nutrient / negative regulation of autophagy / positive regulation of translation / 14-3-3 protein binding / VEGFR2 mediated vascular permeability / positive regulation of peptidyl-threonine phosphorylation / Regulation of PTEN gene transcription Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.67 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 | 7peb.cif.gz | 663.3 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7peb.ent.gz | 536.9 KB | Display | PDB format |
PDBx/mmJSON format | 7peb.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/pe/7peb ftp://data.pdbj.org/pub/pdb/validation_reports/pe/7peb | HTTPS FTP |
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-Related structure data
Related structure data | 13351MC 7pe7C 7pe8C 7pe9C 7peaC 7pecC 7pedC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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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.) Homo sapiens (human) / Gene: MTOR, FRAP, FRAP1, FRAP2, RAFT1, RAPT1 / Production host: Spodoptera frugiperda (fall armyworm) 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.) Homo sapiens (human) / Gene: MLST8, GBL, LST8 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: Q9BVC4 |
#3: Protein | Mass: 155963.094 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: RPTOR, KIAA1303, RAPTOR / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: Q8N122 |
#4: Protein | Mass: 46365.832 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: DEPTOR, DEPDC6 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: Q8TB45 |
#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 |
-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: Homo sapiens (human) | ||||||||||||||||||||||||||||||
Source (recombinant) | Organism: Spodoptera frugiperda (fall armyworm) | ||||||||||||||||||||||||||||||
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 |
-Electron microscopy imaging
Microscopy | Model: TFS GLACIOS |
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Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 200 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELDBright-field microscopy |
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) |
-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: 3.67 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 850152 / Symmetry type: POINT | ||||||||||||||||||||||||||||
Atomic model building | PDB-ID: 6BCX | ||||||||||||||||||||||||||||
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