+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-30711 | |||||||||
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Title | Masked wing-a region of TSC complex | |||||||||
Map data | masked wing-a region of TSC complex | |||||||||
Sample |
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Function / homology | Function and homology information memory T cell differentiation / : / TSC1-TSC2 complex / Inhibition of TSC complex formation by PKB / regulation of phosphoprotein phosphatase activity / cellular response to decreased oxygen levels / regulation of insulin receptor signaling pathway / : / negative regulation of cilium assembly / regulation of cell-matrix adhesion ...memory T cell differentiation / : / TSC1-TSC2 complex / Inhibition of TSC complex formation by PKB / regulation of phosphoprotein phosphatase activity / cellular response to decreased oxygen levels / regulation of insulin receptor signaling pathway / : / negative regulation of cilium assembly / regulation of cell-matrix adhesion / ATPase inhibitor activity / cardiac muscle cell differentiation / Energy dependent regulation of mTOR by LKB1-AMPK / cell projection organization / negative regulation of ATP-dependent activity / negative regulation of cell size / response to growth factor / regulation of stress fiber assembly / activation of GTPase activity / protein folding chaperone complex / anoikis / negative regulation of TOR signaling / TBC/RABGAPs / negative regulation of mitophagy / regulation of small GTPase mediated signal transduction / AKT phosphorylates targets in the cytosol / negative regulation of macroautophagy / Macroautophagy / negative regulation of Wnt signaling pathway / positive chemotaxis / glucose import / Constitutive Signaling by AKT1 E17K in Cancer / positive regulation of focal adhesion assembly / associative learning / positive regulation of macroautophagy / regulation of endocytosis / negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / phosphatase binding / vesicle-mediated transport / negative regulation of TORC1 signaling / Hsp70 protein binding / cellular response to starvation / myelination / viral process / negative regulation of insulin receptor signaling pathway / lipid droplet / GTPase activator activity / adult locomotory behavior / cell-matrix adhesion / insulin-like growth factor receptor signaling pathway / ciliary basal body / phosphatidylinositol 3-kinase/protein kinase B signal transduction / positive regulation of protein ubiquitination / kidney development / neural tube closure / hippocampus development / TP53 Regulates Metabolic Genes / synapse organization / negative regulation of protein kinase activity / Hsp90 protein binding / response to insulin / protein localization / potassium ion transport / cerebral cortex development / small GTPase binding / positive regulation of GTPase activity / endocytosis / protein import into nucleus / lamellipodium / regulation of translation / heart development / cell cortex / protein-folding chaperone binding / cytoplasmic vesicle / adaptive immune response / cell population proliferation / postsynaptic density / lysosome / negative regulation of translation / protein stabilization / regulation of cell cycle / lysosomal membrane / negative regulation of cell population proliferation / perinuclear region of cytoplasm / Golgi apparatus / protein homodimerization activity / protein-containing complex / membrane / nucleus / plasma membrane / cytosol / cytoplasm Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 4.1 Å | |||||||||
Authors | Yang H / Yu Z / Chen X / Li J / Li N / Cheng J / Gao N / Yuan H / Ye D / Guan K / Xu Y | |||||||||
Citation | Journal: Nat Commun / Year: 2021 Title: Structural insights into TSC complex assembly and GAP activity on Rheb. Authors: Huirong Yang / Zishuo Yu / Xizi Chen / Jiabei Li / Ningning Li / Jiaxuan Cheng / Ning Gao / Hai-Xin Yuan / Dan Ye / Kun-Liang Guan / Yanhui Xu / Abstract: Tuberous sclerosis complex (TSC) integrates upstream stimuli and regulates cell growth by controlling the activity of mTORC1. TSC complex functions as a GTPase-activating protein (GAP) towards small ...Tuberous sclerosis complex (TSC) integrates upstream stimuli and regulates cell growth by controlling the activity of mTORC1. TSC complex functions as a GTPase-activating protein (GAP) towards small GTPase Rheb and inhibits Rheb-mediated activation of mTORC1. Mutations in TSC genes cause tuberous sclerosis. In this study, the near-atomic resolution structure of human TSC complex reveals an arch-shaped architecture, with a 2:2:1 stoichiometry of TSC1, TSC2, and TBC1D7. This asymmetric complex consists of two interweaved TSC1 coiled-coil and one TBC1D7 that spans over the tail-to-tail TSC2 dimer. The two TSC2 GAP domains are symmetrically cradled within the core module formed by TSC2 dimerization domain and central coiled-coil of TSC1. Structural and biochemical analyses reveal TSC2 GAP-Rheb complimentary interactions and suggest a catalytic mechanism, by which an asparagine thumb (N1643) stabilizes γ-phosphate of GTP and accelerate GTP hydrolysis of Rheb. Our study reveals mechanisms of TSC complex assembly and GAP activity. | |||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_30711.map.gz | 24.7 MB | EMDB map data format | |
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Header (meta data) | emd-30711-v30.xml emd-30711.xml | 8.2 KB 8.2 KB | Display Display | EMDB header |
Images | emd_30711.png | 22.6 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-30711 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-30711 | HTTPS FTP |
-Related structure data
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_30711.map.gz / Format: CCP4 / Size: 536.4 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | masked wing-a region of TSC complex | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.356 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Sample components
-Entire : Masked wing-a region of TSC complex
Entire | Name: Masked wing-a region of TSC complex |
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Components |
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-Supramolecule #1: Masked wing-a region of TSC complex
Supramolecule | Name: Masked wing-a region of TSC complex / type: complex / ID: 1 / Parent: 0 |
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Source (natural) | Organism: Homo sapiens (human) |
Recombinant expression | Organism: Homo sapiens (human) |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.4 |
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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy |
Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Average electron dose: 50.0 e/Å2 |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Initial angle assignment | Type: OTHER |
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Final angle assignment | Type: MAXIMUM LIKELIHOOD |
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 4.1 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 131022 |