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Open data
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Basic information
Entry | Database: PDB / ID: 5wbi | ||||||
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Title | Crystal structure of the Arabidopsis thaliana Raptor | ||||||
![]() | Regulatory-associated protein of TOR 1 | ||||||
![]() | PROTEIN BINDING / FRB | ||||||
Function / homology | ![]() maintenance of shoot apical meristem identity / TORC1 complex / embryo development ending in seed dormancy / Cul4-RING E3 ubiquitin ligase complex / TOR signaling / negative regulation of autophagy / kinase binding / cytoplasm Similarity search - Function | ||||||
Biological species | ![]() ![]() | ||||||
Method | ![]() ![]() ![]() | ||||||
![]() | Pavletich, N.P. / Jiang, X. | ||||||
![]() | ![]() Title: Mechanisms of mTORC1 activation by RHEB and inhibition by PRAS40. Authors: Haijuan Yang / Xiaolu Jiang / Buren Li / Hyo J Yang / Meredith Miller / Angela Yang / Ankita Dhar / Nikola P Pavletich / ![]() Abstract: The mechanistic target of rapamycin complex 1 (mTORC1) controls cell growth and metabolism in response to nutrients, energy levels, and growth factors. It contains the atypical kinase mTOR and the ...The mechanistic target of rapamycin complex 1 (mTORC1) controls cell growth and metabolism in response to nutrients, energy levels, and growth factors. It contains the atypical kinase mTOR and the RAPTOR subunit that binds to the Tor signalling sequence (TOS) motif of substrates and regulators. mTORC1 is activated by the small GTPase RHEB (Ras homologue enriched in brain) and inhibited by PRAS40. Here we present the 3.0 ångström cryo-electron microscopy structure of mTORC1 and the 3.4 ångström structure of activated RHEB-mTORC1. RHEB binds to mTOR distally from the kinase active site, yet causes a global conformational change that allosterically realigns active-site residues, accelerating catalysis. Cancer-associated hyperactivating mutations map to structural elements that maintain the inactive state, and we provide biochemical evidence that they mimic RHEB relieving auto-inhibition. We also present crystal structures of RAPTOR-TOS motif complexes that define the determinants of TOS recognition, of an mTOR FKBP12-rapamycin-binding (FRB) domain-substrate complex that establishes a second substrate-recruitment mechanism, and of a truncated mTOR-PRAS40 complex that reveals PRAS40 inhibits both substrate-recruitment sites. These findings help explain how mTORC1 selects its substrates, how its kinase activity is controlled, and how it is activated by cancer-associated mutations. | ||||||
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 434.8 KB | Display | ![]() |
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PDB format | ![]() | 354.1 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 439 KB | Display | ![]() |
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Full document | ![]() | 451.4 KB | Display | |
Data in XML | ![]() | 35.7 KB | Display | |
Data in CIF | ![]() | 48.6 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7086C ![]() 7087C ![]() 5wbhC ![]() 5wbjC ![]() 5wbkC ![]() 5wblC ![]() 5wbuC ![]() 5wbyC ![]() 6bcuC ![]() 6bcxC C: citing same article ( |
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Similar structure data |
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Assembly
Deposited unit | ![]()
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Unit cell |
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Components
#1: Protein | Mass: 141855.172 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() Production host: Insect cell expression vector pTIE1 (others) References: UniProt: Q93YQ1 |
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-Experimental details
-Experiment
Experiment | Method: ![]() |
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Sample preparation
Crystal | Density Matthews: 2.37 Å3/Da / Density % sol: 48.13 % / Mosaicity: 0.714 ° |
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Crystal grow | Temperature: 289 K / Method: vapor diffusion, hanging drop / pH: 7 / Details: tacsimate |
-Data collection
Diffraction | Mean temperature: 100 K | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Diffraction source | Source: ![]() ![]() ![]() | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Detector | Type: ADSC QUANTUM 315 / Detector: CCD / Date: Feb 12, 2014 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation wavelength | Wavelength: 0.9792 Å / Relative weight: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection | Resolution: 3→50 Å / Num. obs: 27193 / % possible obs: 97.4 % / Redundancy: 3.1 % / Rmerge(I) obs: 0.086 / Rpim(I) all: 0.057 / Rrim(I) all: 0.104 / Χ2: 1.763 / Net I/σ(I): 12.9 / Num. measured all: 83089 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection shell | Diffraction-ID: 1
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Processing
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Refinement | Method to determine structure: ![]()
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Solvent computation | Ion probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1 Å / Solvent model: MASK | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 74.967 Å2
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Refinement step | Cycle: 1 / Resolution: 3→20 Å
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Refine LS restraints |
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