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- EMDB-3213: Architecture of human mTOR Complex 1 - 5.9 Angstrom reconstruction -
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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-3213 | |||||||||
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Title | Architecture of human mTOR Complex 1 - 5.9 Angstrom reconstruction | |||||||||
![]() | Human mTOR complex 1 | |||||||||
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![]() | Rapamycin / TOR / mTOR / Raptor / mLST8 / FKBP / mTORC1 | |||||||||
Function / homology | ![]() 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 / cellular response to leucine starvation / TFIIIC-class transcription factor complex binding / TORC2 complex ...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 / cellular response to leucine starvation / TFIIIC-class transcription factor complex binding / TORC2 complex / regulation of membrane permeability / heart valve morphogenesis / negative regulation of lysosome organization / RNA polymerase III type 3 promoter sequence-specific DNA binding / positive regulation of transcription of nucleolar large rRNA by RNA polymerase I / TORC1 complex / calcineurin-NFAT signaling cascade / nucleus localization / cellular response to methionine / regulation of osteoclast differentiation / voluntary musculoskeletal movement / positive regulation of odontoblast differentiation / TORC1 signaling / positive regulation of keratinocyte migration / cellular response to L-leucine / MTOR signalling / Amino acids regulate mTORC1 / cellular response to nutrient / regulation of autophagosome assembly / Energy dependent regulation of mTOR by LKB1-AMPK / energy reserve metabolic process / negative regulation of cell size / ruffle organization / protein serine/threonine kinase inhibitor activity / positive regulation of osteoclast differentiation / cellular response to osmotic stress / negative regulation of protein localization to nucleus / enzyme-substrate adaptor activity / anoikis / cardiac muscle cell development / positive regulation of transcription by RNA polymerase III / negative regulation of calcineurin-NFAT signaling cascade / regulation of myelination / negative regulation of macroautophagy / regulation of cell size / positive regulation of G1/S transition of mitotic cell cycle / positive regulation of oligodendrocyte differentiation / Macroautophagy / positive regulation of actin filament polymerization / lysosome organization / positive regulation of myotube differentiation / protein kinase activator activity / oligodendrocyte differentiation / behavioral response to pain / Constitutive Signaling by AKT1 E17K in Cancer / germ cell development / mTORC1-mediated signalling / CD28 dependent PI3K/Akt signaling / : / social behavior / HSF1-dependent transactivation / neuronal action potential / TOR signaling / positive regulation of TOR signaling / response to amino acid / endomembrane system / cellular response to nutrient levels / positive regulation of translational initiation / regulation of macroautophagy / 'de novo' pyrimidine nucleobase biosynthetic process / positive regulation of lamellipodium assembly / positive regulation of epithelial to mesenchymal transition / positive regulation of lipid biosynthetic process / heart morphogenesis / response to nutrient / cardiac muscle contraction / regulation of cellular response to heat / phagocytic vesicle / positive regulation of stress fiber assembly / cytoskeleton organization / 14-3-3 protein binding / Regulation of PTEN gene transcription / positive regulation of endothelial cell proliferation / T cell costimulation / cellular response to starvation / phosphorylation / positive regulation of glycolytic process / cellular response to amino acid starvation / protein serine/threonine kinase activator activity / response to nutrient levels / negative regulation of autophagy / cellular response to amino acid stimulus / VEGFR2 mediated vascular permeability / post-embryonic development / positive regulation of peptidyl-threonine phosphorylation / regulation of signal transduction by p53 class mediator / regulation of autophagy / positive regulation of translation / regulation of circadian rhythm / regulation of cell growth Similarity search - Function | |||||||||
Biological species | ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 5.9 Å | |||||||||
![]() | Aylett CHS / Sauer E / Imseng S / Boehringer D / Hall MN / Ban N / Maier T | |||||||||
![]() | ![]() Title: Architecture of human mTOR complex 1. Authors: Christopher H S Aylett / Evelyn Sauer / Stefan Imseng / Daniel Boehringer / Michael N Hall / Nenad Ban / Timm Maier / ![]() Abstract: Target of rapamycin (TOR), a conserved protein kinase and central controller of cell growth, functions in two structurally and functionally distinct complexes: TORC1 and TORC2. Dysregulation of ...Target of rapamycin (TOR), a conserved protein kinase and central controller of cell growth, functions in two structurally and functionally distinct complexes: TORC1 and TORC2. Dysregulation of mammalian TOR (mTOR) signaling is implicated in pathologies that include diabetes, cancer, and neurodegeneration. We resolved the architecture of human mTORC1 (mTOR with subunits Raptor and mLST8) bound to FK506 binding protein (FKBP)-rapamycin, by combining cryo-electron microscopy at 5.9 angstrom resolution with crystallographic studies of Chaetomium thermophilum Raptor at 4.3 angstrom resolution. The structure explains how FKBP-rapamycin and architectural elements of mTORC1 limit access to the recessed active site. Consistent with a role in substrate recognition and delivery, the conserved amino-terminal domain of Raptor is juxtaposed to the kinase active site. | |||||||||
History |
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Structure visualization
Movie |
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Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 58.6 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 12.3 KB 12.3 KB | Display Display | ![]() |
Images | ![]() | 98.3 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 5flcMC ![]() 3212C ![]() 5ef5C M: atomic model generated by this map C: citing same article ( |
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Similar structure data |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Annotation | Human mTOR complex 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.39 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
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Sample components
-Entire : Human mTOR complex 1
Entire | Name: Human mTOR complex 1 |
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Components |
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-Supramolecule #1000: Human mTOR complex 1
Supramolecule | Name: Human mTOR complex 1 / type: sample / ID: 1000 / Oligomeric state: tetrameric / Number unique components: 3 |
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Molecular weight | Theoretical: 1 MDa |
-Macromolecule #1: mTOR
Macromolecule | Name: mTOR / type: protein_or_peptide / ID: 1 / Oligomeric state: Dimeric / Recombinant expression: Yes |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 290 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | UniProtKB: Serine/threonine-protein kinase mTOR |
-Macromolecule #2: Raptor
Macromolecule | Name: Raptor / type: protein_or_peptide / ID: 2 / Oligomeric state: Dimeric / Recombinant expression: Yes |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 150 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | UniProtKB: Regulatory-associated protein of mTOR |
-Macromolecule #3: mLST8
Macromolecule | Name: mLST8 / type: protein_or_peptide / ID: 3 / Recombinant expression: Yes |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 40 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | UniProtKB: Target of rapamycin complex subunit LST8 |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Buffer | pH: 8 / Details: 100 mM NaCl, 10 mM NaBicine, 1 mM TCEP |
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Grid | Details: Quantifoil R2/2 with an additional thin carbon layer |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 120 K / Instrument: FEI VITROBOT MARK I / Method: 4 second blotting |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Temperature | Average: 100 K |
Alignment procedure | Legacy - Astigmatism: Objective lens astigmatism was corrected at 150,000 times magnification |
Date | May 5, 2015 |
Image recording | Category: CCD / Film or detector model: FEI FALCON II (4k x 4k) / Number real images: 6299 / Average electron dose: 25 e/Å2 Details: Single movie frame readout. 7 frames per exposure. Drift corrected in post-processing. 4 images per hole. Bits/pixel: 16 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Calibrated magnification: 100719 / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 4.0 µm / Nominal defocus min: 1.9 µm / Nominal magnification: 59000 |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
Details | Poor quality micrographs were rejected by eye, based on the extent and regularity of the Thon rings observed in the contrast transfer function. Estimation of the contrast transfer function was carried out for each image using CTFFIND3, particles were selected semi-automatically using boxer and batchboxer. |
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CTF correction | Details: Each image |
Final reconstruction | Applied symmetry - Point group: C2 (2 fold cyclic) / Algorithm: OTHER / Resolution.type: BY AUTHOR / Resolution: 5.9 Å / Resolution method: OTHER / Software - Name: CTFFIND3, RELION, 1.3 Details: For full details see the supplemental materials and methods in the accompanying publication which provides processing details and the classification schema. Number images used: 309792 |