+
Open data
-
Basic information
Entry | Database: PDB / ID: 7dl2 | ||||||
---|---|---|---|---|---|---|---|
Title | Cryo-EM structure of human TSC complex | ||||||
![]() |
| ||||||
![]() | GENE REGULATION / TSC complex / Regulator of cell growth / GTPase-activating protein / Elongated arch-shaped fold | ||||||
Function / homology | ![]() 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 ...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 / negative regulation of ATP-dependent activity / Energy dependent regulation of mTOR by LKB1-AMPK / cell projection organization / 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 / Macroautophagy / negative regulation of macroautophagy / positive chemotaxis / negative regulation of Wnt signaling pathway / glucose import / Constitutive Signaling by AKT1 E17K in Cancer / positive regulation of focal adhesion assembly / associative learning / positive regulation of macroautophagy / regulation of endocytosis / phosphatase binding / negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / ribosomal subunit export from nucleus / vesicle-mediated transport / negative regulation of TORC1 signaling / Hsp70 protein binding / myelination / negative regulation of insulin receptor signaling pathway / viral process / cellular response to starvation / lipid droplet / adult locomotory behavior / phosphatidylinositol 3-kinase/protein kinase B signal transduction / GTPase activator activity / cell-matrix adhesion / insulin-like growth factor receptor signaling pathway / ciliary basal body / positive regulation of GTPase activity / 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 / potassium ion transport / response to insulin / protein localization / cerebral cortex development / small GTPase binding / 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 / protein stabilization / negative regulation of translation / regulation of cell cycle / negative regulation of cell population proliferation / lysosomal membrane / perinuclear region of cytoplasm / Golgi apparatus / protein homodimerization activity / protein-containing complex / membrane / nucleus / plasma membrane / cytoplasm / cytosol Similarity search - Function | ||||||
Biological species | ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 4.4 Å | ||||||
![]() | Yang, H. / Yu, Z. / Chen, X. / Li, J. / Li, N. / Cheng, J. / Gao, N. / Yuan, H. / Ye, D. / Guan, K. / Xu, Y. | ||||||
![]() | ![]() 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 |
|
-
Structure visualization
Movie |
![]() |
---|---|
Structure viewer | Molecule: ![]() ![]() |
-
Downloads & links
-
Download
PDBx/mmCIF format | ![]() | 583.7 KB | Display | ![]() |
---|---|---|---|---|
PDB format | ![]() | 433 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 926.4 KB | Display | ![]() |
---|---|---|---|---|
Full document | ![]() | 1 MB | Display | |
Data in XML | ![]() | 95.5 KB | Display | |
Data in CIF | ![]() | 143.2 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 30708MC M: map data used to model this data C: citing same article ( |
---|---|
Similar structure data |
-
Links
-
Assembly
Deposited unit | ![]()
|
---|---|
1 |
|
-
Components
#1: Protein | Mass: 129945.367 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() #2: Protein | Mass: 188182.312 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() #3: Protein | | Mass: 30911.129 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() #4: Protein | | Mass: 22230.297 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Details: The author does not know what chain F is derived from. Source: (gene. exp.) ![]() ![]() Sequence details | The author does not know the sequence of chain F. | |
---|
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
---|---|
EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-
Sample preparation
Component | Name: Cryo-EM structure of human TSC complex / Type: COMPLEX / Entity ID: all / Source: RECOMBINANT |
---|---|
Source (natural) | Organism: ![]() |
Source (recombinant) | Organism: ![]() |
Buffer solution | pH: 7.4 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
-
Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
---|---|
Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD |
Image recording | Electron dose: 50 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
-
Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
---|---|
3D reconstruction | Resolution: 4.4 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 131022 / Symmetry type: POINT |