[English] 日本語
Yorodumi
- PDB-9v80: Cryo-EM structure of KICSTOR CCC complex (state 4) -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 9v80
TitleCryo-EM structure of KICSTOR CCC complex (state 4)
Components
  • KICSTOR complex protein ITFG2
  • KICSTOR complex protein SZT2
  • KICSTOR complex protein kaptin
KeywordsSIGNALING PROTEIN / lipid binding protein
Function / homology
Function and homology information


regulation of superoxide dismutase activity / KICSTOR complex / corpus callosum morphogenesis / germinal center B cell differentiation / protein localization to lysosome / regulation of TOR signaling / Amino acids regulate mTORC1 / postsynaptic actin cytoskeleton / stereocilium / pigmentation ...regulation of superoxide dismutase activity / KICSTOR complex / corpus callosum morphogenesis / germinal center B cell differentiation / protein localization to lysosome / regulation of TOR signaling / Amino acids regulate mTORC1 / postsynaptic actin cytoskeleton / stereocilium / pigmentation / cellular response to glucose starvation / negative regulation of TORC1 signaling / cellular response to amino acid starvation / actin filament organization / central nervous system development / post-embryonic development / actin filament binding / peroxisome / lamellipodium / lysosomal membrane / intracellular membrane-bounded organelle / glutamatergic synapse / Golgi apparatus / nucleoplasm / cytosol
Similarity search - Function
Kaptin / Integrin-alpha FG-GAP repeat-containing protein 2 / Integrin-alpha FG-GAP repeat-containing protein 2 / Protein SZT2 / Integrin alpha, N-terminal / WD40-repeat-containing domain superfamily
Similarity search - Domain/homology
KICSTOR complex protein SZT2 / KICSTOR complex protein ITFG2 / KICSTOR complex protein kaptin
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.95 Å
AuthorsSu, M.-Y.
Funding support China, 1items
OrganizationGrant numberCountry
Other government20231120103446003 China
CitationJournal: Nat Struct Mol Biol / Year: 2025
Title: Architecture of the human KICSTOR and GATOR1-KICSTOR complexes.
Authors: Fei Teng / Huan Zeng / Xinyi Mai / Shujun Chen / Lulu Wang / Zeming Feng / Shuyun Tian / Shan Wang / Goran Stjepanovic / Chun-Yan Lim / Ming-Yuan Su /
Abstract: The human KICSTOR complex, comprising KPTN, ITFG2, C12orf66 and the scaffolding protein SZT2, anchors the mTORC1 inhibitor GATOR1 to lysosomes. Mutations affecting KICSTOR subunits are associated ...The human KICSTOR complex, comprising KPTN, ITFG2, C12orf66 and the scaffolding protein SZT2, anchors the mTORC1 inhibitor GATOR1 to lysosomes. Mutations affecting KICSTOR subunits are associated with severe neurodevelopmental and epileptic disorders. Loss of KICSTOR mimics GATOR1 inactivation, resulting in constitutive mTORC1 activation, highlighting its critical role in nutrient sensing. Here, we used cryo-electron microscopy and computational modeling to determine the architectures of KICSTOR and the GATOR1-KICSTOR supercomplex. We show that SZT2 forms a crescent-shaped scaffold with repetitive tandem units, binding the ITFG2-KPTN heterodimer and C12orf66 at its C terminus. Structural and biochemical analyses revealed that GATOR1 binds the SZT2 N-terminal domain through NPRL3; disruption of this interaction hyperactivates mTORC1 and mislocalizes TFE3 independently of nutrient status. We further demonstrate the membrane-binding ability of KICSTOR, with SZT2 and C12orf66 preferentially interacting with negatively charged lipids-a requirement for lysosomal localization. These findings identify how KICSTOR positions GATOR1 on lysosomes to regulate nutrient-dependent mTORC1 signaling.
History
DepositionMay 28, 2025Deposition site: PDBJ / Processing site: PDBC
Revision 1.0Nov 12, 2025Provider: repository / Type: Initial release
Revision 1.0Nov 12, 2025Data content type: EM metadata / Data content type: EM metadata / Provider: repository / Type: Initial release
Revision 1.0Nov 12, 2025Data content type: Half map / Part number: 1 / Data content type: Half map / Provider: repository / Type: Initial release
Revision 1.0Nov 12, 2025Data content type: Half map / Part number: 2 / Data content type: Half map / Provider: repository / Type: Initial release
Revision 1.0Nov 12, 2025Data content type: Image / Data content type: Image / Provider: repository / Type: Initial release
Revision 1.0Nov 12, 2025Data content type: Mask / Part number: 1 / Data content type: Mask / Provider: repository / Type: Initial release
Revision 1.0Nov 12, 2025Data content type: Primary map / Data content type: Primary map / Provider: repository / Type: Initial release
Revision 1.1Nov 19, 2025Group: Data collection / Database references / Category: citation / citation_author / em_admin
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year / _em_admin.last_update

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: KICSTOR complex protein SZT2
B: KICSTOR complex protein ITFG2
C: KICSTOR complex protein kaptin


Theoretical massNumber of molelcules
Total (without water)475,9473
Polymers475,9473
Non-polymers00
Water00
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: electron microscopy, not applicable
TypeNameSymmetry operationNumber
identity operation1_5551

-
Components

#1: Protein KICSTOR complex protein SZT2 / Seizure threshold 2 protein homolog


Mass: 378453.438 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
#2: Protein KICSTOR complex protein ITFG2 / Integrin-alpha FG-GAP repeat-containing protein 2


Mass: 49365.742 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: ITFG2 / Production host: Homo sapiens (human) / References: UniProt: Q969R8
#3: Protein KICSTOR complex protein kaptin / Actin-associated protein 2E4


Mass: 48128.305 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: KPTN / Production host: Homo sapiens (human) / References: UniProt: Q9Y664
Has protein modificationN

-
Experimental details

-
Experiment

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

-
Sample preparation

ComponentName: KICSTOR CCC complex / Type: COMPLEX / Entity ID: all / Source: RECOMBINANT
Molecular weightValue: 0.28 MDa / Experimental value: NO
Source (natural)Organism: Homo sapiens (human)
Source (recombinant)Organism: Homo sapiens (human)
Buffer solutionpH: 7.4
SpecimenEmbedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
VitrificationCryogen name: ETHANE

-
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: OTHER
Electron lensMode: BRIGHT FIELD / Nominal defocus max: 1800 nm / Nominal defocus min: 1200 nm
Image recordingElectron dose: 57.65 e/Å2 / Film or detector model: GATAN K3 (6k x 4k)

-
Processing

EM softwareName: PHENIX / Category: model refinement
CTF correctionType: NONE
3D reconstructionResolution: 2.95 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 271421 / Symmetry type: POINT
RefinementStereochemistry target values: REAL-SPACE (WEIGHTED MAP SUM AT ATOM CENTERS)
Refine LS restraints
Refine-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.0049803
ELECTRON MICROSCOPYf_angle_d0.66213352
ELECTRON MICROSCOPYf_dihedral_angle_d6.9641392
ELECTRON MICROSCOPYf_chiral_restr0.0431560
ELECTRON MICROSCOPYf_plane_restr0.0051724

+
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