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- PDB-5wby: Crystal structure of mTOR(deltaN)-mLST8-PRAS40(beta-strand) complex -
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Basic information
Entry | Database: PDB / ID: 5wby | ||||||
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Title | Crystal structure of mTOR(deltaN)-mLST8-PRAS40(beta-strand) complex | ||||||
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![]() | TRANSFERASE / WD40 / PRAS40 beta / complex | ||||||
Function / homology | ![]() positive regulation of cytoplasmic translational initiation / positive regulation of pentose-phosphate shunt / RNA polymerase III type 1 promoter sequence-specific DNA binding / RNA polymerase III type 2 promoter sequence-specific DNA binding / T-helper 1 cell lineage commitment / regulation of locomotor rhythm / positive regulation of wound healing, spreading of epidermal cells / cellular response to leucine starvation / regulation of membrane permeability / TFIIIC-class transcription factor complex binding ...positive regulation of cytoplasmic translational initiation / positive regulation of pentose-phosphate shunt / RNA polymerase III type 1 promoter sequence-specific DNA binding / RNA polymerase III type 2 promoter sequence-specific DNA binding / T-helper 1 cell lineage commitment / regulation of locomotor rhythm / positive regulation of wound healing, spreading of epidermal cells / cellular response to leucine starvation / regulation of membrane permeability / TFIIIC-class transcription factor complex binding / heart valve morphogenesis / negative regulation of lysosome organization / RNA polymerase III type 3 promoter sequence-specific DNA binding / TORC2 complex / TORC1 complex / positive regulation of transcription of nucleolar large rRNA by RNA polymerase I / regulation of autophagosome assembly / calcineurin-NFAT signaling cascade / nucleus localization / TORC1 signaling / 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 / negative regulation of cell size / ruffle organization / protein serine/threonine kinase inhibitor activity / cellular response to osmotic stress / negative regulation of protein localization to nucleus / anoikis / cardiac muscle cell development / negative regulation of TOR signaling / positive regulation of transcription by RNA polymerase III / AKT phosphorylates targets in the cytosol / negative regulation of calcineurin-NFAT signaling cascade / regulation of myelination / regulation of cell size / Macroautophagy / positive regulation of oligodendrocyte differentiation / negative regulation of macroautophagy / positive regulation of actin filament polymerization / lysosome organization / positive regulation of myotube differentiation / protein kinase inhibitor activity / behavioral response to pain / oligodendrocyte differentiation / Constitutive Signaling by AKT1 E17K in Cancer / mTORC1-mediated signalling / germ cell development / CD28 dependent PI3K/Akt signaling / cellular response to nutrient levels / positive regulation of phosphoprotein phosphatase activity / neurotrophin TRK receptor signaling pathway / HSF1-dependent transactivation / positive regulation of TOR signaling / TOR signaling / neuronal action potential / positive regulation of translational initiation / response to amino acid / regulation of macroautophagy / endomembrane system / 'de novo' pyrimidine nucleobase biosynthetic process / regulation of neuron apoptotic process / positive regulation of lamellipodium assembly / positive regulation of epithelial to mesenchymal transition / positive regulation of lipid biosynthetic process / heart morphogenesis / cardiac muscle contraction / regulation of cellular response to heat / positive regulation of stress fiber assembly / negative regulation of TORC1 signaling / cytoskeleton organization / T cell costimulation / cellular response to amino acid starvation / phagocytic vesicle / positive regulation of glycolytic process / cellular response to starvation / negative regulation of autophagy / protein serine/threonine kinase activator activity / response to nutrient levels / response to nutrient / post-embryonic development / VEGFR2 mediated vascular permeability / regulation of signal transduction by p53 class mediator / Regulation of PTEN gene transcription / positive regulation of translation / regulation of cell growth / regulation of actin cytoskeleton organization / TP53 Regulates Metabolic Genes / macroautophagy / phosphoprotein binding / cellular response to amino acid stimulus / negative regulation of protein kinase activity / protein destabilization / protein catabolic process Similarity search - Function | ||||||
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![]() | Pavletich, N.P. / Yang, H. | ||||||
![]() | ![]() 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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-Validation report
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Data in XML | ![]() | 86.4 KB | Display | |
Data in CIF | ![]() | 118.3 KB | Display | |
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-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 ( |
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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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