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Open data
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Basic information
| Entry | Database: PDB / ID: 9o5a | |||||||||||||||
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| Title | The KICSTOR-GATOR1 complex | |||||||||||||||
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Keywords | CELL CYCLE / Lysosome / GATOR1 / KICSTOR / cell growth / amino acid sensing / mTOR / KPTN / ITFG2 / C12orf66 / SZT2 / NPRL2 / NPRL3 / DEPDC5 | |||||||||||||||
| Function / homology | Function and homology informationregulation of superoxide dismutase activity / KICSTOR complex / GATOR1 complex / negative regulation of kinase activity / corpus callosum morphogenesis / aorta morphogenesis / germinal center B cell differentiation / protein localization to lysosome / regulation of TOR signaling / Amino acids regulate mTORC1 ...regulation of superoxide dismutase activity / KICSTOR complex / GATOR1 complex / negative regulation of kinase activity / corpus callosum morphogenesis / aorta morphogenesis / germinal center B cell differentiation / protein localization to lysosome / regulation of TOR signaling / Amino acids regulate mTORC1 / stereocilium / postsynaptic actin cytoskeleton / cardiac muscle tissue development / vacuolar membrane / ventricular septum development / pigmentation / roof of mouth development / cellular response to glucose starvation / intercellular bridge / negative regulation of TORC1 signaling / positive regulation of autophagy / GTPase activator activity / cellular response to amino acid starvation / actin filament organization / central nervous system development / post-embryonic development / small GTPase binding / actin filament binding / peroxisome / lamellipodium / lysosome / intracellular signal transduction / intracellular membrane-bounded organelle / lysosomal membrane / protein-containing complex binding / perinuclear region of cytoplasm / glutamatergic synapse / Golgi apparatus / nucleoplasm / cytosol Similarity search - Function | |||||||||||||||
| Biological species | Homo sapiens (human) | |||||||||||||||
| Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.2 Å | |||||||||||||||
Authors | Bayly-Jones, C. / Lupton, C.J. / Chang, Y.G. / Ellisdon, A.M. | |||||||||||||||
| Funding support | Australia, 4items
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Citation | Journal: Cell / Year: 2026Title: Structure of the lysosomal KICSTOR-GATOR1-SAMTOR nutrient-sensing supercomplex. Authors: Christopher J Lupton / Charles Bayly-Jones / Shuqi Dong / Terrance Lam / Wentong Luo / Gareth D Jones / Chantel Mastos / Nicholas J Frescher / San S Lim / Alastair C Keen / Luke E Formosa / ...Authors: Christopher J Lupton / Charles Bayly-Jones / Shuqi Dong / Terrance Lam / Wentong Luo / Gareth D Jones / Chantel Mastos / Nicholas J Frescher / San S Lim / Alastair C Keen / Luke E Formosa / Hari Venugopal / Yong-Gang Chang / Michelle L Halls / Andrew M Ellisdon / ![]() Abstract: The guanosine triphosphate (GTP)-bound state of the heterodimeric Rag GTPases functions as a molecular switch regulating mechanistic target of rapamycin complex 1 (mTORC1) activation at the lysosome ...The guanosine triphosphate (GTP)-bound state of the heterodimeric Rag GTPases functions as a molecular switch regulating mechanistic target of rapamycin complex 1 (mTORC1) activation at the lysosome downstream of amino acid fluctuations. Under low amino acid conditions, GTPase-activating protein (GAP) activity toward Rags 1 (GATOR1) promotes RagA GTP hydrolysis, preventing mTORC1 activation. KICSTOR recruits and regulates GATOR1 at the lysosome by undefined mechanisms. Here, we resolve the KICSTOR-GATOR1 structure, revealing a striking ∼60-nm crescent-shaped assembly. GATOR1 anchors to KICSTOR via an extensive interface, and mutations that disrupt this interaction impair mTORC1 regulation. The S-adenosylmethionine sensor SAMTOR binds KICSTOR in a manner incompatible with metabolite binding, providing structural insight into methionine sensing via SAMTOR-KICSTOR association. We discover that KICSTOR and GATOR1 form a dimeric supercomplex. This assembly restricts GATOR1 to an orientation that favors the low-affinity active GAP mode of Rag GTPase engagement while sterically restricting access to the high-affinity inhibitory mode, consistent with a model of an active lysosomal GATOR1 docking complex. | |||||||||||||||
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Structure visualization
| Structure viewer | Molecule: Molmil Jmol/JSmol |
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Downloads & links
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Download
| PDBx/mmCIF format | 9o5a.cif.gz | 1.1 MB | Display | PDBx/mmCIF format |
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| PDB format | pdb9o5a.ent.gz | 865.2 KB | Display | PDB format |
| PDBx/mmJSON format | 9o5a.json.gz | Tree view | PDBx/mmJSON format | |
| Others | Other downloads |
-Validation report
| Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/o5/9o5a ftp://data.pdbj.org/pub/pdb/validation_reports/o5/9o5a | HTTPS FTP |
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-Related structure data
| Related structure data | ![]() 70135MC ![]() 9o5dC ![]() 9o5eC C: citing same article ( M: map data used to model this data |
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| Similar structure data | Similarity search - Function & homology F&H Search |
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Links
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Assembly
| Deposited unit | ![]()
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Components
-GATOR complex protein ... , 2 types, 2 molecules HC
| #1: Protein | Mass: 45799.547 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Details: N-terminal HA tagged NPRL2 / Source: (gene. exp.) Homo sapiens (human) / Gene: NPRL2, TUSC4 / Production host: Homo sapiens (human) / References: UniProt: Q8WTW4 |
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| #7: Protein | Mass: 65769.000 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Details: N-terminal HA tagged NPRL3 / Source: (gene. exp.) Homo sapiens (human) / Gene: NPRL3, C16orf35, CGTHBA, MARE / Production host: Homo sapiens (human) / References: UniProt: Q12980 |
-Protein , 2 types, 2 molecules BF
| #2: Protein | Mass: 183207.703 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Details: N-terminal FLAG tagged DEPDC5 / Source: (gene. exp.) Homo sapiens (human) / Gene: DEPDC5, KIAA0645 / Production host: Homo sapiens (human) / References: UniProt: O75140 |
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| #5: Protein | Mass: 52573.930 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Details: N-terminal HA tagged C12orf66 / Source: (gene. exp.) Homo sapiens (human) / Gene: KICS2, C12orf66 / Production host: Homo sapiens (human) / References: UniProt: Q96MD2 |
-KICSTOR complex protein ... , 3 types, 3 molecules DEG
| #3: Protein | Mass: 380386.500 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: SZT2, C1orf84, KIAA0467 / Production host: Homo sapiens (human) / References: UniProt: Q5T011 |
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| #4: Protein | Mass: 50216.473 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Details: N-terminal HA tagged KPTN / Source: (gene. exp.) Homo sapiens (human) / Gene: KPTN / Production host: Homo sapiens (human) / References: UniProt: Q9Y664 |
| #6: Protein | Mass: 51270.758 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Details: N-terminal myc tagged ITFG2 / Source: (gene. exp.) Homo sapiens (human) / Gene: ITFG2 / Production host: Homo sapiens (human) / References: UniProt: Q969R8 |
-Details
| Has protein modification | N |
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-Experimental details
-Experiment
| Experiment | Method: ELECTRON MICROSCOPY |
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| EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
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| Buffer solution | pH: 7.4 | ||||||||||||||||||||||||
| Specimen | Conc.: 0.68 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||||||
| Specimen support | Grid material: COPPER / Grid mesh size: 200 divisions/in. / Grid type: Quantifoil R1.2/1.3 | ||||||||||||||||||||||||
| Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 278 K |
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Electron microscopy imaging
| Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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| Microscopy | Model: TFS KRIOS |
| Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
| Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 1800 nm / Nominal defocus min: 500 nm |
| Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
| Image recording | Electron dose: 1 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
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Processing
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| CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | |||||||||||||||
| Symmetry | Point symmetry: C1 (asymmetric) | |||||||||||||||
| 3D reconstruction | Resolution: 3.2 Å / Resolution method: OTHER / Num. of particles: 43700 Details: Resolution estimated as the average nominal resolution of constituent focused refinements. See focused reconstructions. Symmetry type: POINT | |||||||||||||||
| Atomic model building | Protocol: FLEXIBLE FIT |
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Homo sapiens (human)
Australia, 4items
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FIELD EMISSION GUN