[English] 日本語
Yorodumi
- PDB-6cet: Cryo-EM structure of GATOR1 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6cet
TitleCryo-EM structure of GATOR1
Components
  • GATOR complex protein DEPDC5
  • GATOR complex protein NPRL2
  • GATOR complex protein NPRL3
KeywordsSIGNALING PROTEIN / mTORC1 amino-acid sensing lysosome growth control
Function / homology
Function and homology information


GATOR1 complex / aorta morphogenesis / TORC1 signaling / Amino acids regulate mTORC1 / cardiac muscle tissue development / negative regulation of TOR signaling / vacuolar membrane / ventricular septum development / negative regulation of kinase activity / roof of mouth development ...GATOR1 complex / aorta morphogenesis / TORC1 signaling / Amino acids regulate mTORC1 / cardiac muscle tissue development / negative regulation of TOR signaling / vacuolar membrane / ventricular septum development / negative regulation of kinase activity / roof of mouth development / positive regulation of autophagy / negative regulation of TORC1 signaling / cellular response to amino acid starvation / GTPase activator activity / small GTPase binding / lysosome / intracellular signal transduction / lysosomal membrane / protein-containing complex binding / perinuclear region of cytoplasm / cytosol
Similarity search - Function
: / Nitrogen permease regulator 3 / Nitrogen permease regulator 2 / Vacuolar membrane-associated protein Iml1 / DEPDC5 protein, C-terminal / Nitrogen Permease regulator of amino acid transport activity 3 / Nitrogen permease regulator 2 / Vacuolar membrane-associated protein Iml1, N-terminal domain / DEPDC5 protein C-terminal region / Domain found in Dishevelled, Egl-10, and Pleckstrin (DEP) ...: / Nitrogen permease regulator 3 / Nitrogen permease regulator 2 / Vacuolar membrane-associated protein Iml1 / DEPDC5 protein, C-terminal / Nitrogen Permease regulator of amino acid transport activity 3 / Nitrogen permease regulator 2 / 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 / Winged helix DNA-binding domain superfamily / Winged helix-like DNA-binding domain superfamily
Similarity search - Domain/homology
GATOR1 complex protein DEPDC5 / GATOR1 complex protein NPRL3 / GATOR1 complex protein NPRL2
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 4.4 Å
AuthorsShen, K. / Huang, R.K. / Brignole, E.J. / Yu, Z. / Sabatini, D.M.
Funding support United States, 7items
OrganizationGrant numberCountry
National Institutes of Health/National Cancer Institute (NIH/NCI)R01 CA103866 United States
National Institutes of Health/National Cancer Institute (NIH/NCI)R01 CA129105 United States
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)R37 AI47389 United States
Department of Defense (DOD, United States)W81XWH-15-1-0230 United States
National Science Foundation (NSF, United States)2016197106 United States
Howard Hughes Medical Institute (HHMI) United States
Life Sciences Research Foundation United States
CitationJournal: Nature / Year: 2018
Title: Architecture of the human GATOR1 and GATOR1-Rag GTPases complexes.
Authors: Kuang Shen / Rick K Huang / Edward J Brignole / Kendall J Condon / Max L Valenstein / Lynne Chantranupong / Aimaiti Bomaliyamu / Abigail Choe / Chuan Hong / Zhiheng Yu / David M Sabatini /
Abstract: Nutrients, such as amino acids and glucose, signal through the Rag GTPases to activate mTORC1. The GATOR1 protein complex-comprising DEPDC5, NPRL2 and NPRL3-regulates the Rag GTPases as a GTPase- ...Nutrients, such as amino acids and glucose, signal through the Rag GTPases to activate mTORC1. The GATOR1 protein complex-comprising DEPDC5, NPRL2 and NPRL3-regulates the Rag GTPases as a GTPase-activating protein (GAP) for RAGA; loss of GATOR1 desensitizes mTORC1 signalling to nutrient starvation. GATOR1 components have no sequence homology to other proteins, so the function of GATOR1 at the molecular level is currently unknown. Here we used cryo-electron microscopy to solve structures of GATOR1 and GATOR1-Rag GTPases complexes. GATOR1 adopts an extended architecture with a cavity in the middle; NPRL2 links DEPDC5 and NPRL3, and DEPDC5 contacts the Rag GTPase heterodimer. Biochemical analyses reveal that our GATOR1-Rag GTPases structure is inhibitory, and that at least two binding modes must exist between the Rag GTPases and GATOR1. Direct interaction of DEPDC5 with RAGA inhibits GATOR1-mediated stimulation of GTP hydrolysis by RAGA, whereas weaker interactions between the NPRL2-NPRL3 heterodimer and RAGA execute GAP activity. These data reveal the structure of a component of the nutrient-sensing mTORC1 pathway and a non-canonical interaction between a GAP and its substrate GTPase.
History
DepositionFeb 12, 2018Deposition site: RCSB / Processing site: RCSB
Revision 1.0Mar 28, 2018Provider: repository / Type: Initial release
Revision 1.1Apr 11, 2018Group: Data collection / Database references / Category: citation / citation_author
Item: _citation.pdbx_database_id_PubMed / _citation.title / _citation_author.name
Revision 1.2Apr 18, 2018Group: Data collection / Database references / Category: citation
Item: _citation.journal_volume / _citation.page_first / _citation.page_last
Revision 1.3Feb 20, 2019Group: Author supporting evidence / Data collection / Category: pdbx_audit_support / Item: _pdbx_audit_support.funding_organization
Revision 1.4Apr 10, 2019Group: Author supporting evidence / Data collection / Category: pdbx_audit_support / Item: _pdbx_audit_support.funding_organization
Revision 1.5Nov 20, 2019Group: Author supporting evidence / Category: pdbx_audit_support / Item: _pdbx_audit_support.funding_organization
Revision 1.6Nov 27, 2019Group: Author supporting evidence / Category: pdbx_audit_support / Item: _pdbx_audit_support.funding_organization
Revision 1.7Dec 18, 2019Group: Other / Category: atom_sites
Item: _atom_sites.fract_transf_matrix[1][1] / _atom_sites.fract_transf_matrix[2][2] / _atom_sites.fract_transf_matrix[3][3]
Revision 1.8Mar 13, 2024Group: Data collection / Database references / Category: chem_comp_atom / chem_comp_bond / database_2
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession

-
Structure visualization

Movie
  • Deposited structure unit
  • Imaged by Jmol
  • Download
  • Superimposition on EM map
  • EMDB-7465
  • Imaged by UCSF Chimera
  • Download
Movie viewer
Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
N: GATOR complex protein NPRL2
M: GATOR complex protein NPRL3
D: GATOR complex protein DEPDC5


Theoretical massNumber of molelcules
Total (without water)288,8703
Polymers288,8703
Non-polymers00
Water00
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_5551

-
Components

#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: 43711.395 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: NPRL2, TUSC4 / Cell line (production host): 293F / Production host: Homo sapiens (human) / References: UniProt: Q8WTW4
#2: 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: 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 / Cell line (production host): 293F / Production host: Homo sapiens (human) / References: UniProt: Q12980
#3: Protein GATOR complex protein DEPDC5 / DEP domain-containing protein 5


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 / Cell line (production host): 293F / Production host: Homo sapiens (human) / References: UniProt: O75140

-
Experimental details

-
Experiment

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

-
Sample preparation

ComponentName: GATOR1 / Type: COMPLEX / Entity ID: all / Source: MULTIPLE SOURCES
Molecular weightValue: 0.29 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: FEI TITAN KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELD
Image recordingElectron dose: 55 e/Å2 / Detector mode: SUPER-RESOLUTION / Film or detector model: GATAN K2 QUANTUM (4k x 4k)

-
Processing

SoftwareName: PHENIX / Version: 1.12_2829: / Classification: refinement
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
SymmetryPoint symmetry: C1 (asymmetric)
3D reconstructionResolution: 4.4 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 309773 / Symmetry type: POINT
Refine LS restraints
Refine-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.00813993
ELECTRON MICROSCOPYf_angle_d1.35918970
ELECTRON MICROSCOPYf_dihedral_angle_d10.6858424
ELECTRON MICROSCOPYf_chiral_restr0.0672122
ELECTRON MICROSCOPYf_plane_restr0.012428

+
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://pdbjlvh1.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