+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-20660 | |||||||||||||||||||||||||||
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Title | Raptor-Rag-Ragulator complex | |||||||||||||||||||||||||||
Map data | Unmasked, unsharpened. | |||||||||||||||||||||||||||
Sample |
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Keywords | signaling complex / GTPase / lysosome / SIGNALING PROTEIN | |||||||||||||||||||||||||||
Function / homology | Function and homology information regulation of cholesterol import / positive regulation of protein localization to lysosome / regulation of cell-substrate junction organization / Gtr1-Gtr2 GTPase complex / regulation of cholesterol efflux / positive regulation of RNA polymerase II regulatory region sequence-specific DNA binding / FNIP-folliculin RagC/D GAP / Ragulator complex / protein localization to cell junction / positive regulation of pentose-phosphate shunt ...regulation of cholesterol import / positive regulation of protein localization to lysosome / regulation of cell-substrate junction organization / Gtr1-Gtr2 GTPase complex / regulation of cholesterol efflux / positive regulation of RNA polymerase II regulatory region sequence-specific DNA binding / FNIP-folliculin RagC/D GAP / Ragulator complex / protein localization to cell junction / positive regulation of pentose-phosphate shunt / regulation of TORC1 signaling / TORC1 complex / protein localization to lysosome / regulation of TOR signaling / positive regulation of odontoblast differentiation / TORC1 signaling / endosome organization / fibroblast migration / cellular response to L-leucine / MTOR signalling / Amino acids regulate mTORC1 / lysosome localization / Energy dependent regulation of mTOR by LKB1-AMPK / kinase activator activity / protein localization to membrane / protein serine/threonine kinase inhibitor activity / positive regulation of osteoclast differentiation / cellular response to osmotic stress / enzyme-substrate adaptor activity / positive regulation of transcription by RNA polymerase III / endosomal transport / azurophil granule membrane / regulation of cell size / small GTPase-mediated signal transduction / positive regulation of G1/S transition of mitotic cell cycle / Macroautophagy / lysosome organization / protein kinase activator activity / RHOJ GTPase cycle / RHOQ GTPase cycle / mTORC1-mediated signalling / tertiary granule membrane / CDC42 GTPase cycle / social behavior / RHOH GTPase cycle / ficolin-1-rich granule membrane / HSF1-dependent transactivation / RHOG GTPase cycle / TOR signaling / regulation of receptor recycling / positive regulation of TOR signaling / RAC2 GTPase cycle / RAC3 GTPase cycle / response to amino acid / cellular response to nutrient levels / specific granule membrane / positive regulation of lipid biosynthetic process / protein-membrane adaptor activity / 14-3-3 protein binding / Regulation of PTEN gene transcription / tumor necrosis factor-mediated signaling pathway / positive regulation of endothelial cell proliferation / RAC1 GTPase cycle / positive regulation of TORC1 signaling / cellular response to starvation / positive regulation of glycolytic process / cellular response to amino acid starvation / viral genome replication / negative regulation of autophagy / cellular response to amino acid stimulus / RNA splicing / negative regulation of cysteine-type endopeptidase activity involved in apoptotic process / guanyl-nucleotide exchange factor activity / positive regulation of peptidyl-threonine phosphorylation / regulation of autophagy / cholesterol homeostasis / positive regulation of interleukin-8 production / regulation of cell growth / TP53 Regulates Metabolic Genes / cellular response to glucose stimulus / phosphoprotein binding / Hydrolases; Acting on acid anhydrides; Acting on GTP to facilitate cellular and subcellular movement / MAP2K and MAPK activation / response to virus / small GTPase binding / positive regulation of protein localization to nucleus / cytoplasmic stress granule / GDP binding / positive regulation of peptidyl-serine phosphorylation / protein localization / glucose homeostasis / late endosome / E3 ubiquitin ligases ubiquitinate target proteins / GTPase binding / late endosome membrane / cellular response to hypoxia / positive regulation of NF-kappaB transcription factor activity / positive regulation of cell growth / protein-macromolecule adaptor activity / positive regulation of canonical NF-kappaB signal transduction Similarity search - Function | |||||||||||||||||||||||||||
Biological species | Homo sapiens (human) | |||||||||||||||||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.18 Å | |||||||||||||||||||||||||||
Authors | Rogala KB / Sabatini DM | |||||||||||||||||||||||||||
Funding support | United States, United Kingdom, 8 items
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Citation | Journal: Science / Year: 2019 Title: Structural basis for the docking of mTORC1 on the lysosomal surface. Authors: Kacper B Rogala / Xin Gu / Jibril F Kedir / Monther Abu-Remaileh / Laura F Bianchi / Alexia M S Bottino / Rikke Dueholm / Anna Niehaus / Daan Overwijn / Ange-Célia Priso Fils / Sherry X ...Authors: Kacper B Rogala / Xin Gu / Jibril F Kedir / Monther Abu-Remaileh / Laura F Bianchi / Alexia M S Bottino / Rikke Dueholm / Anna Niehaus / Daan Overwijn / Ange-Célia Priso Fils / Sherry X Zhou / Daniel Leary / Nouf N Laqtom / Edward J Brignole / David M Sabatini / Abstract: The mTORC1 (mechanistic target of rapamycin complex 1) protein kinase regulates growth in response to nutrients and growth factors. Nutrients promote its translocation to the lysosomal surface, where ...The mTORC1 (mechanistic target of rapamycin complex 1) protein kinase regulates growth in response to nutrients and growth factors. Nutrients promote its translocation to the lysosomal surface, where its Raptor subunit interacts with the Rag guanosine triphosphatase (GTPase)-Ragulator complex. Nutrients switch the heterodimeric Rag GTPases among four different nucleotide-binding states, only one of which (RagA/B•GTP-RagC/D•GDP) permits mTORC1 association. We used cryo-electron microscopy to determine the structure of the supercomplex of Raptor with Rag-Ragulator at a resolution of 3.2 angstroms. Our findings indicate that the Raptor α-solenoid directly detects the nucleotide state of RagA while the Raptor "claw" threads between the GTPase domains to detect that of RagC. Mutations that disrupted Rag-Raptor binding inhibited mTORC1 lysosomal localization and signaling. By comparison with a structure of mTORC1 bound to its activator Rheb, we developed a model of active mTORC1 docked on the lysosome. | |||||||||||||||||||||||||||
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_20660.map.gz | 132 MB | EMDB map data format | |
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Header (meta data) | emd-20660-v30.xml emd-20660.xml | 24 KB 24 KB | Display Display | EMDB header |
Images | emd_20660.png | 120 KB | ||
Filedesc metadata | emd-20660.cif.gz | 7.6 KB | ||
Others | emd_20660_additional.map.gz | 154.5 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-20660 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-20660 | HTTPS FTP |
-Validation report
Summary document | emd_20660_validation.pdf.gz | 549.9 KB | Display | EMDB validaton report |
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Full document | emd_20660_full_validation.pdf.gz | 549.5 KB | Display | |
Data in XML | emd_20660_validation.xml.gz | 6.7 KB | Display | |
Data in CIF | emd_20660_validation.cif.gz | 7.6 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-20660 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-20660 | HTTPS FTP |
-Related structure data
Related structure data | 6u62MC C: citing same article (ref.) M: atomic model generated by this map |
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Similar 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_20660.map.gz / Format: CCP4 / Size: 166.4 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | Unmasked, unsharpened. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.059 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Additional map: Unmasked, sharpened.
File | emd_20660_additional.map | ||||||||||||
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Annotation | Unmasked, sharpened. | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
+Entire : Raptor-Rag-Ragulator
+Supramolecule #1: Raptor-Rag-Ragulator
+Macromolecule #1: Regulatory-associated protein of mTOR
+Macromolecule #2: Ras-related GTP-binding protein A
+Macromolecule #3: Ras-related GTP-binding protein C
+Macromolecule #4: Ragulator complex protein LAMTOR1
+Macromolecule #5: Ragulator complex protein LAMTOR2
+Macromolecule #6: Ragulator complex protein LAMTOR3
+Macromolecule #7: Ragulator complex protein LAMTOR4
+Macromolecule #8: Ragulator complex protein LAMTOR5
+Macromolecule #9: GUANOSINE-5'-TRIPHOSPHATE
+Macromolecule #10: MAGNESIUM ION
+Macromolecule #11: GUANOSINE-5'-DIPHOSPHATE
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.5 |
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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Average electron dose: 42.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Startup model | Type of model: PDB ENTRY |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.18 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 112037 |
Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |