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Open data
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Basic information
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| Title | GATOR2 complex bound to arginine sensor CASTOR1 | |||||||||
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Keywords | Complex / mTORC1 / Signaling / Nutrients / Amino Acid Sensing / SIGNALING PROTEIN | |||||||||
| Function / homology | Function and homology informationoligodendrocyte progenitor proliferation / GATOR2 complex / cellular response to L-arginine / molecular sensor activity / Seh1-associated complex / COPII-coated vesicle budding / protein exit from endoplasmic reticulum / positive regulation of ER to Golgi vesicle-mediated transport / nuclear pore outer ring / nuclear pore organization ...oligodendrocyte progenitor proliferation / GATOR2 complex / cellular response to L-arginine / molecular sensor activity / Seh1-associated complex / COPII-coated vesicle budding / protein exit from endoplasmic reticulum / positive regulation of ER to Golgi vesicle-mediated transport / nuclear pore outer ring / nuclear pore organization / COPII-coated vesicle cargo loading / central nervous system myelin formation / COPII vesicle coat / Nuclear Pore Complex (NPC) Disassembly / Regulation of Glucokinase by Glucokinase Regulatory Protein / Defective TPR may confer susceptibility towards thyroid papillary carcinoma (TPC) / Transport of Ribonucleoproteins into the Host Nucleus / positive regulation of protein exit from endoplasmic reticulum / attachment of mitotic spindle microtubules to kinetochore / Transport of the SLBP independent Mature mRNA / Transport of the SLBP Dependant Mature mRNA / Amino acids regulate mTORC1 / SUMOylation of SUMOylation proteins / Transport of Mature mRNA Derived from an Intronless Transcript / NS1 Mediated Effects on Host Pathways / Rev-mediated nuclear export of HIV RNA / Nuclear import of Rev protein / SUMOylation of RNA binding proteins / NEP/NS2 Interacts with the Cellular Export Machinery / protein K6-linked ubiquitination / Transport of Mature mRNA derived from an Intron-Containing Transcript / oligodendrocyte differentiation / tRNA processing in the nucleus / Postmitotic nuclear pore complex (NPC) reformation / arginine binding / COPII-mediated vesicle transport / protein-containing complex localization / vacuolar membrane / nucleocytoplasmic transport / Viral Messenger RNA Synthesis / SUMOylation of ubiquitinylation proteins / Vpr-mediated nuclear import of PICs / positive regulation of macroautophagy / SUMOylation of DNA replication proteins / Regulation of HSF1-mediated heat shock response / mitotic metaphase chromosome alignment / positive regulation of TOR signaling / mRNA transport / SUMOylation of DNA damage response and repair proteins / negative regulation of TORC1 signaling / Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal / positive regulation of TORC1 signaling / MHC class II antigen presentation / signaling adaptor activity / cellular response to nutrient levels / Mitotic Prometaphase / EML4 and NUDC in mitotic spindle formation / cellular response to amino acid starvation / Resolution of Sister Chromatid Cohesion / SUMOylation of chromatin organization proteins / protein localization to plasma membrane / regulation of autophagy / HCMV Late Events / Antigen Presentation: Folding, assembly and peptide loading of class I MHC / protein sequestering activity / ER to Golgi transport vesicle membrane / RHO GTPases Activate Formins / protein import into nucleus / intracellular protein transport / RING-type E3 ubiquitin transferase / ISG15 antiviral mechanism / kinetochore / autophagy / HCMV Early Events / Separation of Sister Chromatids / ubiquitin protein ligase activity / nuclear envelope / protein transport / snRNP Assembly / cell division / lysosomal membrane / endoplasmic reticulum membrane / SARS-CoV-2 activates/modulates innate and adaptive immune responses / structural molecule activity / endoplasmic reticulum / extracellular exosome / nucleoplasm / zinc ion binding / identical protein binding / cytosol / cytoplasm Similarity search - Function | |||||||||
| Biological species | Homo sapiens (human) | |||||||||
| Method | single particle reconstruction / cryo EM / Resolution: 3.5 Å | |||||||||
Authors | Jansen RM / Hurley JH | |||||||||
| Funding support | United States, 1 items
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Citation | Journal: Nat Struct Mol Biol / Year: 2025Title: Structural basis for mTORC1 regulation by the CASTOR1-GATOR2 complex. Authors: Rachel M Jansen / Clément Maghe / Karla Tapia / Selina Wu / Serim Yang / Xuefeng Ren / Roberto Zoncu / James H Hurley / ![]() Abstract: Mechanistic target of rapamycin complex 1 (mTORC1) is a nutrient-responsive master regulator of metabolism. Amino acids control the recruitment and activation of mTORC1 at the lysosome through the ...Mechanistic target of rapamycin complex 1 (mTORC1) is a nutrient-responsive master regulator of metabolism. Amino acids control the recruitment and activation of mTORC1 at the lysosome through the nucleotide loading state of the heterodimeric Rag GTPases. Under low nutrients, including arginine, the GTPase-activating protein complex GATOR1 promotes GTP hydrolysis on RagA/B, inactivating mTORC1. GATOR1 is regulated by the cage-like GATOR2 complex and cytosolic amino acid sensors. To understand how the arginine sensor CASTOR1 binds to GATOR2 to disinhibit GATOR1 under low cytosolic arginine, we determined the cryo-electron microscopy structure of human GATOR2 bound to CASTOR1 in the absence of arginine. Two MIOS WD40 domain β-propellers of the GATOR2 cage engage with both subunits of a single CASTOR1 homodimer. Each propeller binds to a negatively charged MIOS-binding interface on CASTOR1 that is distal to the arginine pocket. The structure shows how arginine-triggered loop ordering in CASTOR1 blocks the MIOS-binding interface, switches off its binding to GATOR2 and, thus, communicates to downstream mTORC1 activation. | |||||||||
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Structure visualization
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Downloads & links
-EMDB archive
| Map data | emd_70833.map.gz | 609.3 MB | EMDB map data format | |
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| Header (meta data) | emd-70833-v30.xml emd-70833.xml | 27.9 KB 27.9 KB | Display Display | EMDB header |
| Images | emd_70833.png | 56 KB | ||
| Filedesc metadata | emd-70833.cif.gz | 9 KB | ||
| Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-70833 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-70833 | HTTPS FTP |
-Related structure data
| Related structure data | ![]() 9otiMC C: citing same article ( M: atomic model generated by this map |
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| Similar structure data | Similarity search - Function & homology F&H Search |
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Links
| EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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| Related items in Molecule of the Month |
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Map
| File | Download / File: emd_70833.map.gz / Format: CCP4 / Size: 669.9 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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| Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
| Voxel size | X=Y=Z: 1.05 Å | ||||||||||||||||||||||||||||||||||||
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| Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
| Details | EMDB XML:
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-Supplemental data
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Sample components
+Entire : GATOR2 complex bound to arginine sensor CASTOR1
+Supramolecule #1: GATOR2 complex bound to arginine sensor CASTOR1
+Supramolecule #2: GATOR2 Complex
+Supramolecule #3: CASTOR1
+Macromolecule #1: GATOR2 complex protein MIOS
+Macromolecule #2: GATOR complex protein WDR24
+Macromolecule #3: GATOR complex protein WDR59
+Macromolecule #4: Nucleoporin SEH1
+Macromolecule #5: Protein SEC13 homolog
+Macromolecule #6: Cytosolic arginine sensor for mTORC1 subunit 1
+Macromolecule #7: ZINC ION
-Experimental details
-Structure determination
| Method | cryo EM |
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Processing | single particle reconstruction |
| Aggregation state | particle |
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Sample preparation
| Buffer | pH: 7.5 |
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| Vitrification | Cryogen name: ETHANE |
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Electron microscopy
| Microscope | TFS KRIOS |
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| Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 50.0 e/Å2 |
| Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
| Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.0 µm / Nominal defocus min: 1.0 µm |
| Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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About Yorodumi




Keywords
Homo sapiens (human)
Authors
United States, 1 items
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Processing
FIELD EMISSION GUN

