[English] 日本語
Yorodumi
- PDB-9o5a: The KICSTOR-GATOR1 complex -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 9o5a
TitleThe KICSTOR-GATOR1 complex
Components
  • (GATOR complex protein ...) x 2
  • (KICSTOR complex protein ...) x 3
  • GATOR1 complex protein DEPDC5
  • KICSTOR subunit 2
KeywordsCELL CYCLE / Lysosome / GATOR1 / KICSTOR / cell growth / amino acid sensing / mTOR / KPTN / ITFG2 / C12orf66 / SZT2 / NPRL2 / NPRL3 / DEPDC5
Function / homology
Function and homology information


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 ...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
KICSTOR subunit 2 / KICSTOR complex protein C12orf66-like, central domain superfamily / KICSTOR complex C12orf66 like / Kaptin / Integrin-alpha FG-GAP repeat-containing protein 2 / Integrin-alpha FG-GAP repeat-containing protein 2 / Protein SZT2 / : / IML1 N-terminal double psi beta barrel domain / Nitrogen permease regulator 3 ...KICSTOR subunit 2 / KICSTOR complex protein C12orf66-like, central domain superfamily / KICSTOR complex C12orf66 like / Kaptin / Integrin-alpha FG-GAP repeat-containing protein 2 / Integrin-alpha FG-GAP repeat-containing protein 2 / Protein SZT2 / : / IML1 N-terminal double psi beta barrel domain / Nitrogen permease regulator 3 / Nitrogen permease regulator 2 / : / Nitrogen Permease regulator of amino acid transport activity 3 / Nitrogen permease regulator 2 / GATOR1 complex protein NPRL3, C-terminal HTH / Vacuolar membrane-associated protein Iml1 / DEPDC5 protein, C-terminal / : / Vacuolar membrane-associated protein Iml1, N-terminal domain / DEPDC5 protein C-terminal region / Domain found in Dishevelled, Egl-10, and Pleckstrin (DEP) / DEP domain profile. / Domain found in Dishevelled, Egl-10, and Pleckstrin / DEP domain / Integrin alpha, N-terminal / Winged helix DNA-binding domain superfamily / Winged helix-like DNA-binding domain superfamily / WD40-repeat-containing domain superfamily
Similarity search - Domain/homology
GATOR1 complex protein DEPDC5 / GATOR1 complex protein NPRL3 / KICSTOR complex protein SZT2 / GATOR1 complex protein NPRL2 / KICSTOR complex protein ITFG2 / KICSTOR subunit 2 / KICSTOR complex protein kaptin
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.2 Å
AuthorsBayly-Jones, C. / Lupton, C.J. / Chang, Y.G. / Ellisdon, A.M.
Funding support Australia, 4items
OrganizationGrant numberCountry
National Health and Medical Research Council (NHMRC, Australia)APP2036864 Australia
Australian Research Council (ARC)DE240100992 Australia
Other governmentMCRF21036 Australia
Australian Research Council (ARC)LE170100016 Australia
CitationJournal: Cell / Year: 2026
Title: 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.
History
DepositionApr 9, 2025Deposition site: RCSB / Processing site: RCSB
Revision 1.0Feb 18, 2026Provider: repository / Type: Initial release
Revision 1.0Feb 18, 2026Data content type: EM metadata / Data content type: EM metadata / Provider: repository / Type: Initial release
Revision 1.0Feb 18, 2026Data content type: Image / Data content type: Image / Provider: repository / Type: Initial release
Revision 1.0Feb 18, 2026Data content type: Primary map / Data content type: Primary map / Provider: repository / Type: Initial release

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
H: GATOR complex protein NPRL2
B: GATOR1 complex protein DEPDC5
D: KICSTOR complex protein SZT2
E: KICSTOR complex protein kaptin
F: KICSTOR subunit 2
G: KICSTOR complex protein ITFG2
C: GATOR complex protein NPRL3


Theoretical massNumber of molelcules
Total (without water)829,2247
Polymers829,2247
Non-polymers00
Water00
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: electron microscopy, A consensus reconstruction, as well as focused 2D classifications support the placement of focused refinements.
TypeNameSymmetry operationNumber
identity operation1_5551

-
Components

-
GATOR complex protein ... , 2 types, 2 molecules HC

#1: Protein GATOR complex protein NPRL2 / Gene 21 protein / G21 protein / Nitrogen permease regulator 2-like protein / NPR2-like protein / ...Gene 21 protein / G21 protein / Nitrogen permease regulator 2-like protein / NPR2-like protein / Tumor suppressor candidate 4


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
#7: Protein GATOR complex protein NPRL3 / -14 gene protein / Alpha-globin regulatory element-containing gene protein / Nitrogen permease ...-14 gene protein / Alpha-globin regulatory element-containing gene protein / Nitrogen permease regulator 3-like protein / Protein CGTHBA


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 GATOR1 complex protein DEPDC5 / DEP domain-containing protein 5


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
#5: Protein KICSTOR subunit 2 / KICSTOR complex protein C12orf66


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 KICSTOR complex protein SZT2 / Seizure threshold 2 protein homolog


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
#4: Protein KICSTOR complex protein kaptin / Actin-associated protein 2E4


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 KICSTOR complex protein ITFG2 / Integrin-alpha FG-GAP repeat-containing protein 2


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 modificationN

-
Experimental details

-
Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction

-
Sample preparation

Component
IDNameTypeEntity IDParent-IDSource
1Binary complex of KICSTOR-GATOR1COMPLEXall0RECOMBINANT
2GATOR1 subcomplexCOMPLEX#1-#2, #71RECOMBINANT
3KICSTOR subcomplexCOMPLEX#3-#61RECOMBINANT
Molecular weight
IDEntity assembly-IDValue (°)Experimental value
110.82 MDaYES
210.298 MDaYES
Source (natural)
IDEntity assembly-IDOrganismNcbi tax-ID
21Homo sapiens (human)9606
32Homo sapiens (human)9606
43Homo sapiens (human)9606
Source (recombinant)
IDEntity assembly-IDOrganismNcbi tax-ID
21Homo sapiens (human)9606
32Homo sapiens (human)9606
43Homo sapiens (human)9606
Buffer solutionpH: 7.4
SpecimenConc.: 0.68 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
Specimen supportGrid material: COPPER / Grid mesh size: 200 divisions/in. / Grid type: Quantifoil R1.2/1.3
VitrificationInstrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 278 K

-
Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyModel: TFS KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELD / Nominal defocus max: 1800 nm / Nominal defocus min: 500 nm
Specimen holderCryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER
Image recordingElectron dose: 1 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k)

-
Processing

EM software
IDNameCategory
1RELIONparticle selection
2cryoSPARCparticle selection
14RELION3D reconstruction
15cryoSPARC3D reconstruction
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
SymmetryPoint symmetry: C1 (asymmetric)
3D reconstructionResolution: 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 buildingProtocol: FLEXIBLE FIT

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242):Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more