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Yorodumi- PDB-5wby: Crystal structure of mTOR(deltaN)-mLST8-PRAS40(beta-strand) complex -
+Open data
-Basic information
Entry | Database: PDB / ID: 5wby | ||||||
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Title | Crystal structure of mTOR(deltaN)-mLST8-PRAS40(beta-strand) complex | ||||||
Components |
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Keywords | TRANSFERASE / WD40 / PRAS40 beta / complex | ||||||
Function / homology | Function and homology information 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 / voluntary musculoskeletal movement / regulation of osteoclast 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 / cellular response to osmotic stress / negative regulation of TOR signaling / negative regulation of protein localization to nucleus / anoikis / cardiac muscle cell development / AKT phosphorylates targets in the cytosol / 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 oligodendrocyte differentiation / Macroautophagy / positive regulation of actin filament polymerization / lysosome organization / positive regulation of myotube differentiation / protein kinase inhibitor 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 / : / neurotrophin TRK receptor signaling pathway / 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 / regulation of neuron apoptotic process / heart morphogenesis / response to nutrient / cardiac muscle contraction / regulation of cellular response to heat / phagocytic vesicle / positive regulation of stress fiber assembly / negative regulation of TORC1 signaling / cytoskeleton organization / Regulation of PTEN gene transcription / 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 / regulation of signal transduction by p53 class mediator / positive regulation of translation / regulation of circadian rhythm / regulation of cell growth / macroautophagy / regulation of actin cytoskeleton organization / TP53 Regulates Metabolic Genes / phosphoprotein binding Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 3.1 Å | ||||||
Authors | Pavletich, N.P. / Yang, H. | ||||||
Citation | Journal: Nature / Year: 2017 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. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 5wby.cif.gz | 1.1 MB | Display | PDBx/mmCIF format |
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PDB format | pdb5wby.ent.gz | 918.3 KB | Display | PDB format |
PDBx/mmJSON format | 5wby.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 5wby_validation.pdf.gz | 485.5 KB | Display | wwPDB validaton report |
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Full document | 5wby_full_validation.pdf.gz | 510.7 KB | Display | |
Data in XML | 5wby_validation.xml.gz | 86.4 KB | Display | |
Data in CIF | 5wby_validation.cif.gz | 118.3 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/wb/5wby ftp://data.pdbj.org/pub/pdb/validation_reports/wb/5wby | HTTPS FTP |
-Related structure data
Related structure data | 7086C 7087C 5wbhC 5wbiC 5wbjC 5wbkC 5wblC 5wbuC 6bcuC 6bcxC 4jsnS S: Starting model for refinement C: citing same article (ref.) |
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Similar structure data |
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-Assembly
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Noncrystallographic symmetry (NCS) | NCS domain:
NCS domain segments: Component-ID: 1 / Refine code: 2
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