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- PDB-5wbk: Crystal structure of the arabidopsis thaliana Raptor in complex w... -
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Basic information
Entry | Database: PDB / ID: 5wbk | ||||||
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Title | Crystal structure of the arabidopsis thaliana Raptor in complex with the TOS peptide of human S6K1 | ||||||
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![]() | PROTEIN BINDING / Raptor / TOS | ||||||
Function / homology | ![]() maintenance of shoot apical meristem identity / long-chain fatty acid import into cell / response to electrical stimulus involved in regulation of muscle adaptation / skeletal muscle atrophy / positive regulation of skeletal muscle tissue growth / regulation of glucose import / ribosomal protein S6 kinase activity / TORC1 complex / embryo development ending in seed dormancy / response to L-leucine ...maintenance of shoot apical meristem identity / long-chain fatty acid import into cell / response to electrical stimulus involved in regulation of muscle adaptation / skeletal muscle atrophy / positive regulation of skeletal muscle tissue growth / regulation of glucose import / ribosomal protein S6 kinase activity / TORC1 complex / embryo development ending in seed dormancy / response to L-leucine / cellular response to nutrient / Cul4-RING E3 ubiquitin ligase complex / response to glucagon / response to testosterone / positive regulation of smooth muscle cell migration / germ cell development / mTORC1-mediated signalling / phosphatidylinositol-mediated signaling / skeletal muscle contraction / TOR signaling / behavioral fear response / positive regulation of translational initiation / response to tumor necrosis factor / long-term memory / response to glucose / response to mechanical stimulus / negative regulation of insulin receptor signaling pathway / positive regulation of TORC1 signaling / protein serine/threonine/tyrosine kinase activity / positive regulation of mitotic cell cycle / response to nutrient levels / negative regulation of autophagy / cellular response to dexamethasone stimulus / protein phosphatase 2A binding / positive regulation of translation / PDZ domain binding / negative regulation of extrinsic apoptotic signaling pathway / positive regulation of smooth muscle cell proliferation / peptide binding / modulation of chemical synaptic transmission / response to toxic substance / cellular response to type II interferon / cellular response to growth factor stimulus / kinase binding / cellular response to insulin stimulus / G1/S transition of mitotic cell cycle / cell migration / peptidyl-serine phosphorylation / response to ethanol / mitochondrial outer membrane / postsynapse / response to lipopolysaccharide / non-specific serine/threonine protein kinase / protein kinase activity / neuron projection / response to xenobiotic stimulus / protein serine kinase activity / protein serine/threonine kinase activity / glutamatergic synapse / negative regulation of apoptotic process / apoptotic process / perinuclear region of cytoplasm / cell surface / signal transduction / mitochondrion / nucleoplasm / ATP binding / identical protein binding / nucleus / cytosol / 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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PDBx/mmCIF format | ![]() | 439.4 KB | Display | ![]() |
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PDB format | ![]() | 359 KB | Display | ![]() |
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-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 7086C ![]() 7087C ![]() 5wbhC ![]() 5wbiSC ![]() 5wbjC ![]() 5wblC ![]() 5wbuC ![]() 5wbyC ![]() 6bcuC ![]() 6bcxC S: Starting model for refinement 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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#2: Protein/peptide | Mass: 1564.670 Da / Num. of mol.: 1 / Fragment: residues 24-37 / Source method: obtained synthetically / Source: (synth.) ![]() References: UniProt: P23443, non-specific serine/threonine protein kinase |
-Experimental details
-Experiment
Experiment | Method: ![]() |
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Sample preparation
Crystal | Density Matthews: 2.69 Å3/Da / Density % sol: 54.2 % / Mosaicity: 0.818 ° |
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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: 3.1→80 Å / Num. obs: 27998 / % possible obs: 99.2 % / Redundancy: 6.5 % / Rmerge(I) obs: 0.084 / Rpim(I) all: 0.035 / Rrim(I) all: 0.091 / Χ2: 0.408 / Net I/σ(I): 5.3 / Num. measured all: 182755 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection shell | Diffraction-ID: 1
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Refinement | Method to determine structure: ![]() Starting model: 5WBI Resolution: 3.11→20 Å / Cor.coef. Fo:Fc: 0.944 / Cor.coef. Fo:Fc free: 0.911 / SU B: 55.101 / SU ML: 0.401 / Cross valid method: THROUGHOUT / ESU R Free: 0.477 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
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Solvent computation | Ion probe radii: 0.9 Å / Shrinkage radii: 0.9 Å / VDW probe radii: 1 Å / Solvent model: MASK | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 104.936 Å2
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Refinement step | Cycle: 1 / Resolution: 3.11→20 Å
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Refine LS restraints |
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