[English] 日本語
Yorodumi
- PDB-9dx0: Human GATOR2 complex - apo state -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 9dx0
TitleHuman GATOR2 complex - apo state
Components
  • GATOR2 complex protein MIOS
  • GATOR2 complex protein WDR24
  • Protein SEC13 homolog
KeywordsSIGNALING PROTEIN / nutrient sensor / mTORC1 pathway
Biological speciesHomo sapiens (human)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.47 Å
AuthorsWranik, M. / Rogala, K.B.
Funding support United States, 5items
OrganizationGrant numberCountry
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)R35 GM150935 United States
National Institutes of Health/National Cancer Institute (NIH/NCI)R00 CA255926 United States
National Institutes of Health/National Cancer Institute (NIH/NCI)P30 CA124435 United States
Department of Defense (DOD, United States)CA220856 United States
Lustgarten Foundation1156790 United States
CitationJournal: Nature / Year: 2025
Title: Structural basis for the dynamic regulation of mTORC1 by amino acids.
Authors: Max L Valenstein / Maximilian Wranik / Pranav V Lalgudi / Karen Y Linde-Garelli / Yuri Choi / Raghu R Chivukula / David M Sabatini / Kacper B Rogala /
Abstract: The mechanistic target of rapamycin complex 1 (mTORC1) anchors a conserved signalling pathway that regulates growth in response to nutrient availability. Amino acids activate mTORC1 through the Rag ...The mechanistic target of rapamycin complex 1 (mTORC1) anchors a conserved signalling pathway that regulates growth in response to nutrient availability. Amino acids activate mTORC1 through the Rag GTPases, which are regulated by GATOR, a supercomplex consisting of GATOR1, KICSTOR and the nutrient-sensing hub GATOR2 (refs. ). GATOR2 forms an octagonal cage, with its distinct WD40 domain β-propellers interacting with GATOR1 and the leucine sensors Sestrin1 and Sestrin2 (SESN1 and SESN2) and the arginine sensor CASTOR1 (ref. ). The mechanisms through which these sensors regulate GATOR2 and how they detach from it upon binding their cognate amino acids remain unknown. Here, using cryo-electron microscopy, we determined the structures of a stabilized GATOR2 bound to either Sestrin2 or CASTOR1. The sensors occupy distinct and non-overlapping binding sites, disruption of which selectively impairs the ability of mTORC1 to sense individual amino acids. We also resolved the apo (leucine-free) structure of Sestrin2 and characterized the amino acid-induced structural rearrangements within Sestrin2 and CASTOR1 that trigger their dissociation from GATOR2. Binding of either sensor restricts the dynamic WDR24 β-propeller of GATOR2, a domain essential for nutrient-dependent mTORC1 activation. These findings reveal the allosteric mechanisms that convey amino acid sufficiency to GATOR2 and the ensuing structural changes that lead to mTORC1 activation.
History
DepositionOct 10, 2024Deposition site: RCSB / Processing site: RCSB
Revision 1.0May 20, 2026Provider: repository / Type: Initial release
Revision 1.0May 20, 2026Data content type: EM metadata / Data content type: EM metadata / Provider: repository / Type: Initial release
Revision 1.0May 20, 2026Data content type: Additional map / Part number: 1 / Data content type: Additional map / Provider: repository / Type: Initial release
Revision 1.0May 20, 2026Data content type: Additional map / Part number: 2 / Data content type: Additional map / Provider: repository / Type: Initial release
Revision 1.0May 20, 2026Data content type: Additional map / Part number: 3 / Data content type: Additional map / Provider: repository / Type: Initial release
Revision 1.0May 20, 2026Data content type: Additional map / Part number: 4 / Data content type: Additional map / Provider: repository / Type: Initial release
Revision 1.0May 20, 2026Data content type: Additional map / Part number: 5 / Data content type: Additional map / Provider: repository / Type: Initial release
Revision 1.0May 20, 2026Data content type: Additional map / Part number: 6 / Data content type: Additional map / Provider: repository / Type: Initial release
Revision 1.0May 20, 2026Data content type: Additional map / Part number: 7 / Data content type: Additional map / Provider: repository / Type: Initial release
Revision 1.0May 20, 2026Data content type: Additional map / Part number: 8 / Data content type: Additional map / Provider: repository / Type: Initial release
Revision 1.0May 20, 2026Data content type: Additional map / Part number: 9 / Data content type: Additional map / Provider: repository / Type: Initial release
Revision 1.0May 20, 2026Data content type: Additional map / Part number: 10 / Data content type: Additional map / Provider: repository / Type: Initial release
Revision 1.0May 20, 2026Data content type: Additional map / Part number: 11 / Data content type: Additional map / Provider: repository / Type: Initial release
Revision 1.0May 20, 2026Data content type: Additional map / Part number: 12 / Data content type: Additional map / Provider: repository / Type: Initial release
Revision 1.0May 20, 2026Data content type: Additional map / Part number: 13 / Data content type: Additional map / Provider: repository / Type: Initial release
Revision 1.0May 20, 2026Data content type: Additional map / Part number: 14 / Data content type: Additional map / Provider: repository / Type: Initial release
Revision 1.0May 20, 2026Data content type: Additional map / Part number: 15 / Data content type: Additional map / Provider: repository / Type: Initial release
Revision 1.0May 20, 2026Data content type: Additional map / Part number: 16 / Data content type: Additional map / Provider: repository / Type: Initial release
Revision 1.0May 20, 2026Data content type: Additional map / Part number: 17 / Data content type: Additional map / Provider: repository / Type: Initial release
Revision 1.0May 20, 2026Data content type: Additional map / Part number: 18 / Data content type: Additional map / Provider: repository / Type: Initial release
Revision 1.0May 20, 2026Data content type: Additional map / Part number: 19 / Data content type: Additional map / Provider: repository / Type: Initial release
Revision 1.0May 20, 2026Data content type: Additional map / Part number: 20 / Data content type: Additional map / Provider: repository / Type: Initial release
Revision 1.0May 20, 2026Data content type: Additional map / Part number: 21 / Data content type: Additional map / Provider: repository / Type: Initial release
Revision 1.0May 20, 2026Data content type: Additional map / Part number: 22 / Data content type: Additional map / Provider: repository / Type: Initial release
Revision 1.0May 20, 2026Data content type: Additional map / Part number: 23 / Data content type: Additional map / Provider: repository / Type: Initial release
Revision 1.0May 20, 2026Data content type: Additional map / Part number: 24 / Data content type: Additional map / Provider: repository / Type: Initial release
Revision 1.0May 20, 2026Data content type: Half map / Part number: 1 / Data content type: Half map / Provider: repository / Type: Initial release
Revision 1.0May 20, 2026Data content type: Half map / Part number: 2 / Data content type: Half map / Provider: repository / Type: Initial release
Revision 1.0May 20, 2026Data content type: Image / Data content type: Image / Provider: repository / Type: Initial release
Revision 1.0May 20, 2026Data content type: Mask / Part number: 1 / Data content type: Mask / Provider: repository / Type: Initial release
Revision 1.0May 20, 2026Data content type: Mask / Part number: 2 / Data content type: Mask / Provider: repository / Type: Initial release
Revision 1.0May 20, 2026Data content type: Mask / Part number: 3 / Data content type: Mask / Provider: repository / Type: Initial release
Revision 1.0May 20, 2026Data content type: Mask / Part number: 4 / Data content type: Mask / Provider: repository / Type: Initial release
Revision 1.0May 20, 2026Data content type: Mask / Part number: 5 / Data content type: Mask / Provider: repository / Type: Initial release
Revision 1.0May 20, 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
A: GATOR2 complex protein MIOS
B: GATOR2 complex protein MIOS
C: GATOR2 complex protein WDR24
D: Protein SEC13 homolog


Theoretical massNumber of molelcules
Total (without water)424,5394
Polymers424,5394
Non-polymers00
Water00
1


  • Idetical with deposited unit
  • defined by author
TypeNameSymmetry operationNumber
identity operation1_5551

-
Components

#1: Protein GATOR2 complex protein MIOS


Mass: 125920.211 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Cell line (production host): HEK293F / Production host: Homo sapiens (human)
#2: Protein GATOR2 complex protein WDR24


Mass: 102253.469 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Cell line (production host): HEK293F / Production host: Homo sapiens (human)
#3: Protein Protein SEC13 homolog


Mass: 70445.391 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Cell line (production host): HEK293F / Production host: Homo sapiens (human)
Has protein modificationY

-
Experimental details

-
Experiment

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

-
Sample preparation

ComponentName: Human GATOR2 Complex - Apo State / Type: COMPLEX / Entity ID: all / Source: RECOMBINANT
Molecular weightValue: 1.1 MDa / Experimental value: NO
Source (natural)Organism: Homo sapiens (human)
Source (recombinant)Organism: Homo sapiens (human) / Cell: HEK293F
Buffer solutionpH: 7.4
SpecimenConc.: 3 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
Specimen supportGrid mesh size: 300 divisions/in. / Grid type: Quantifoil R1.2/1.3
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: FLOOD BEAM
Electron lensMode: 4D-STEM / Nominal defocus max: 2100 nm / Nominal defocus min: 500 nm
Image recordingElectron dose: 64.64 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k)

-
Processing

EM software
IDNameVersionCategory
1Topaz0.2.5particle selection
2PHENIX1.21.1_5286model refinement
5CTFFIND4.1.14CTF correction
13cryoSPARC4.53D reconstruction
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
3D reconstructionResolution: 3.47 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 1148926 / Symmetry type: POINT
RefinementHighest resolution: 3.47 Å
Stereochemistry target values: REAL-SPACE (WEIGHTED MAP SUM AT ATOM CENTERS)
Refine LS restraints
Refine-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.00427681
ELECTRON MICROSCOPYf_angle_d0.45637794
ELECTRON MICROSCOPYf_dihedral_angle_d10.0359116
ELECTRON MICROSCOPYf_chiral_restr0.0434328
ELECTRON MICROSCOPYf_plane_restr0.0034858

+
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