+Open data
-Basic information
Entry | Database: PDB / ID: 7t3c | ||||||
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Title | GATOR1-RAG-RAGULATOR - Dual Complex | ||||||
Components |
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Keywords | HYDROLASE / Complex / GTPase activating protein / nutrient sensing / metabolism | ||||||
Function / homology | Function and homology information GATOR1 complex / 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 / aorta morphogenesis ...GATOR1 complex / 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 / aorta morphogenesis / protein localization to cell junction / regulation of TORC1 signaling / protein localization to lysosome / regulation of TOR signaling / TORC1 signaling / endosome organization / fibroblast migration / lysosome localization / Amino acids regulate mTORC1 / MTOR signalling / Energy dependent regulation of mTOR by LKB1-AMPK / protein localization to membrane / kinase activator activity / enzyme-substrate adaptor activity / cardiac muscle tissue development / ventricular septum development / vacuolar membrane / azurophil granule membrane / endosomal transport / small GTPase-mediated signal transduction / regulation of cell size / negative regulation of kinase activity / lysosome organization / Macroautophagy / roof of mouth development / RHOJ GTPase cycle / RHOQ GTPase cycle / mTORC1-mediated signalling / tertiary granule membrane / CDC42 GTPase cycle / ficolin-1-rich granule membrane / RHOH GTPase cycle / RHOG GTPase cycle / positive regulation of TOR signaling / regulation of receptor recycling / RAC2 GTPase cycle / response to amino acid / RAC3 GTPase cycle / cellular response to nutrient levels / specific granule membrane / positive regulation of autophagy / protein-membrane adaptor activity / tumor necrosis factor-mediated signaling pathway / negative regulation of TORC1 signaling / RAC1 GTPase cycle / positive regulation of TORC1 signaling / cellular response to starvation / cellular response to amino acid starvation / GTPase activator activity / RNA splicing / viral genome replication / negative regulation of autophagy / : / cholesterol homeostasis / guanyl-nucleotide exchange factor activity / Regulation of PTEN gene transcription / positive regulation of interleukin-8 production / regulation of cell growth / TP53 Regulates Metabolic Genes / cellular response to amino acid stimulus / phosphoprotein binding / MAP2K and MAPK activation / response to virus / small GTPase binding / positive regulation of protein localization to nucleus / GDP binding / late endosome / protein localization / E3 ubiquitin ligases ubiquitinate target proteins / GTPase binding / late endosome membrane / glucose homeostasis / positive regulation of NF-kappaB transcription factor activity / Hydrolases; Acting on acid anhydrides; Acting on GTP to facilitate cellular and subcellular movement / positive regulation of canonical NF-kappaB signal transduction / positive regulation of MAPK cascade / molecular adaptor activity / lysosome / endosome membrane / intracellular signal transduction / protein heterodimerization activity / membrane raft / lysosomal membrane / intracellular membrane-bounded organelle / focal adhesion / GTPase activity / DNA-templated transcription / ubiquitin protein ligase binding / Neutrophil degranulation / protein-containing complex binding Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 4 Å | ||||||
Authors | Egri, S.B. / Shen, K. | ||||||
Funding support | United States, 1items
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Citation | Journal: Mol Cell / Year: 2022 Title: Cryo-EM structures of the human GATOR1-Rag-Ragulator complex reveal a spatial-constraint regulated GAP mechanism. Authors: Shawn B Egri / Christna Ouch / Hui-Ting Chou / Zhiheng Yu / Kangkang Song / Chen Xu / Kuang Shen / Abstract: mTORC1 controls cellular metabolic processes in response to nutrient availability. Amino acid signals are transmitted to mTORC1 through the Rag GTPases, which are localized on the lysosomal surface ...mTORC1 controls cellular metabolic processes in response to nutrient availability. Amino acid signals are transmitted to mTORC1 through the Rag GTPases, which are localized on the lysosomal surface by the Ragulator complex. The Rag GTPases receive amino acid signals from multiple upstream regulators. One negative regulator, GATOR1, is a GTPase activating protein (GAP) for RagA. GATOR1 binds to the Rag GTPases via two modes: an inhibitory mode and a GAP mode. How these two binding interactions coordinate to process amino acid signals is unknown. Here, we resolved three cryo-EM structural models of the GATOR1-Rag-Ragulator complex, with the Rag-Ragulator subcomplex occupying the inhibitory site, the GAP site, and both binding sites simultaneously. When the Rag GTPases bind to GATOR1 at the GAP site, both Rag subunits contact GATOR1 to coordinate their nucleotide loading states. These results reveal a potential GAP mechanism of GATOR1 during the mTORC1 inactivation process. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7t3c.cif.gz | 741.3 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7t3c.ent.gz | 601.7 KB | Display | PDB format |
PDBx/mmJSON format | 7t3c.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7t3c_validation.pdf.gz | 1.1 MB | Display | wwPDB validaton report |
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Full document | 7t3c_full_validation.pdf.gz | 1.2 MB | Display | |
Data in XML | 7t3c_validation.xml.gz | 110.1 KB | Display | |
Data in CIF | 7t3c_validation.cif.gz | 171.1 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/t3/7t3c ftp://data.pdbj.org/pub/pdb/validation_reports/t3/7t3c | HTTPS FTP |
-Related structure data
Related structure data | 25654MC 7t3aC 7t3bC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
-GATOR complex protein ... , 3 types, 3 molecules BAC
#1: Protein | Mass: 43711.395 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: NPRL2, TUSC4 / Production host: Homo sapiens (human) / References: UniProt: Q8WTW4 |
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#2: Protein | Mass: 181478.000 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: DEPDC5, KIAA0645 / Production host: Homo sapiens (human) / References: UniProt: O75140 |
#8: Protein | Mass: 63680.820 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: NPRL3, C16orf35, CGTHBA, MARE / Production host: Homo sapiens (human) / References: UniProt: Q12980 |
-Ragulator complex protein ... , 5 types, 10 molecules HOGNJQIPFM
#3: Protein | Mass: 13637.678 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: LAMTOR3, MAP2K1IP1, MAPKSP1, PRO2783 / Production host: Homo sapiens (human) / References: UniProt: Q9UHA4 #4: Protein | Mass: 13517.450 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: LAMTOR2, MAPBPIP, ROBLD3, HSPC003 / Production host: Homo sapiens (human) / References: UniProt: Q9Y2Q5 #5: Protein | Mass: 9622.900 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: LAMTOR5, HBXIP, XIP / Production host: Homo sapiens (human) / References: UniProt: O43504 #6: Protein | Mass: 10753.236 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: LAMTOR4, C7orf59 / Production host: Homo sapiens (human) / References: UniProt: Q0VGL1 #7: Protein | Mass: 17762.775 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: LAMTOR1, C11orf59, PDRO, PP7157 / Production host: Homo sapiens (human) / References: UniProt: Q6IAA8 |
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-Ras-related GTP-binding protein ... , 3 types, 4 molecules DKEL
#9: Protein | Mass: 36615.168 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: RRAGA / Production host: Homo sapiens (human) / References: UniProt: Q7L523 #10: Protein | | Mass: 44195.734 Da / Num. of mol.: 1 / Mutation: F92A Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: RRAGC / Production host: Homo sapiens (human) References: UniProt: Q9HB90, Hydrolases; Acting on acid anhydrides; Acting on GTP to facilitate cellular and subcellular movement #11: Protein | | Mass: 44298.859 Da / Num. of mol.: 1 / Mutation: S75N Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: RRAGC / Production host: Homo sapiens (human) / References: UniProt: Q9HB90 |
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-Non-polymers , 2 types, 6 molecules
#12: Chemical | #13: Chemical | |
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-Details
Has ligand of interest | Y |
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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 |
-Sample preparation
Component | Name: GATOR1-RAG-RAGULATOR - Dual Complex / Type: COMPLEX / Entity ID: #1-#11 / Source: RECOMBINANT |
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Source (natural) | Organism: Homo sapiens (human) |
Source (recombinant) | Organism: Homo sapiens (human) |
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 |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: -3000 nm / Nominal defocus min: -1500 nm |
Image recording | Electron dose: 52.6 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
-Processing
Software | Name: PHENIX / Version: 1.18.2_3874: / Classification: refinement | ||||||||||||||||||||||||
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction | Resolution: 4 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 56117 / Symmetry type: POINT | ||||||||||||||||||||||||
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