[English] 日本語
Yorodumi
- PDB-8q7e: Structure of CUL9-RBX1 ubiquitin E3 ligase complex - hexameric as... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8q7e
TitleStructure of CUL9-RBX1 ubiquitin E3 ligase complex - hexameric assembly
Components
  • Cullin-9
  • E3 ubiquitin-protein ligase RBX1
KeywordsLIGASE / Cullin-RING RBR E3 Ligase
Function / homology
Function and homology information


negative regulation of beige fat cell differentiation / cullin-RING-type E3 NEDD8 transferase / NEDD8 transferase activity / negative regulation of mitophagy / cullin-RING ubiquitin ligase complex / regulation of xenophagy / Loss of Function of FBXW7 in Cancer and NOTCH1 Signaling / cellular response to chemical stress / Cul7-RING ubiquitin ligase complex / regulation of cell cycle process ...negative regulation of beige fat cell differentiation / cullin-RING-type E3 NEDD8 transferase / NEDD8 transferase activity / negative regulation of mitophagy / cullin-RING ubiquitin ligase complex / regulation of xenophagy / Loss of Function of FBXW7 in Cancer and NOTCH1 Signaling / cellular response to chemical stress / Cul7-RING ubiquitin ligase complex / regulation of cell cycle process / neural crest cell differentiation / RNA polymerase II transcription initiation surveillance / positive regulation of protein autoubiquitination / protein neddylation / regulation of BMP signaling pathway / NEDD8 ligase activity / regulation of mitophagy / negative regulation of response to oxidative stress / regulation of centrosome duplication / regulation of mitotic nuclear division / protein K27-linked ubiquitination / VCB complex / Cul5-RING ubiquitin ligase complex / regulation of TOR signaling / ubiquitin-ubiquitin ligase activity / ubiquitin-dependent protein catabolic process via the C-end degron rule pathway / Cul2-RING ubiquitin ligase complex / SCF ubiquitin ligase complex / negative regulation of DNA-templated DNA replication / regulation of mitotic cytokinesis / Cul3-RING ubiquitin ligase complex / regulation of DNA damage checkpoint / negative regulation of type I interferon production / regulation of miRNA-mediated gene silencing / regulation of natural killer cell activation / SCF-dependent proteasomal ubiquitin-dependent protein catabolic process / Prolactin receptor signaling / regulation of cell cycle phase transition / Cul4A-RING E3 ubiquitin ligase complex / Cul4-RING E3 ubiquitin ligase complex / regulation of stem cell population maintenance / Cul4B-RING E3 ubiquitin ligase complex / ubiquitin ligase complex scaffold activity / negative regulation of adipose tissue development / regulation of cellular response to stress / limb development / protein monoubiquitination / cullin family protein binding / centrosome duplication / regulation of DNA-templated DNA replication initiation / cilium assembly / ribosome-associated ubiquitin-dependent protein catabolic process / signal transduction in response to DNA damage / negative regulation of insulin receptor signaling pathway / Nuclear events stimulated by ALK signaling in cancer / protein K48-linked ubiquitination / regulation of cellular response to insulin stimulus / positive regulation of TORC1 signaling / transcription-coupled nucleotide-excision repair / post-translational protein modification / cellular response to amino acid stimulus / regulation of embryonic development / replication fork processing / negative regulation of canonical NF-kappaB signal transduction / regulation of mitotic cell cycle / Regulation of BACH1 activity / site of DNA damage / T cell activation / G1/S transition of mitotic cell cycle / negative regulation of canonical Wnt signaling pathway / epigenetic regulation of gene expression / Degradation of DVL / Degradation of CRY and PER proteins / nucleotide-excision repair / Degradation of GLI1 by the proteasome / Recognition of DNA damage by PCNA-containing replication complex / GSK3B and BTRC:CUL1-mediated-degradation of NFE2L2 / Negative regulation of NOTCH4 signaling / regulation of autophagy / microtubule cytoskeleton organization / RING-type E3 ubiquitin transferase / Hedgehog 'on' state / Vif-mediated degradation of APOBEC3G / FBXL7 down-regulates AURKA during mitotic entry and in early mitosis / Degradation of GLI2 by the proteasome / GLI3 is processed to GLI3R by the proteasome / GSK3B-mediated proteasomal degradation of PD-L1(CD274) / Evasion by RSV of host interferon responses / NOTCH1 Intracellular Domain Regulates Transcription / regulation of circadian rhythm / Degradation of beta-catenin by the destruction complex / Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha / DNA Damage Recognition in GG-NER / cell population proliferation / Constitutive Signaling by NOTCH1 PEST Domain Mutants / Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants / Dual Incision in GG-NER / Transcription-Coupled Nucleotide Excision Repair (TC-NER) / Formation of TC-NER Pre-Incision Complex / SPOP-mediated proteasomal degradation of PD-L1(CD274)
Similarity search - Function
: / : / : / : / : / : / CUL7/CUL9, N-terminal beta-barrel domain / CUL7/CUL9 ARM repeat domain / Cullin-9-like, TPR repeats / E3 ubiquitin-protein ligase ARIH2, N-terminal UBA domain ...: / : / : / : / : / : / CUL7/CUL9, N-terminal beta-barrel domain / CUL7/CUL9 ARM repeat domain / Cullin-9-like, TPR repeats / E3 ubiquitin-protein ligase ARIH2, N-terminal UBA domain / CPH domain / Mouse development and cellular proliferation protein Cullin-7 / CPH (CUL7, PARC, and HERC2) domain profile. / IBR domain, a half RING-finger domain / IBR domain / APC10/DOC domain / Anaphase-promoting complex, subunit 10 (APC10) / DOC domain profile. / Anaphase-promoting complex, subunit 10 (APC10) / IBR domain / In Between Ring fingers / TRIAD supradomain / TRIAD supradomain profile. / Zinc finger, RING-H2-type / RING-H2 zinc finger domain / : / Cullin, conserved site / Cullin family signature. / Cullin, N-terminal / Cullin protein, neddylation domain / Cullin / Cullin protein neddylation domain / Cullin alpha solenoid domain / : / Cullin alpha+beta domain / Cullin homology domain / Cullin homology domain superfamily / Cullin family profile. / Zinc finger, RING-type, conserved site / Zinc finger RING-type signature. / Galactose-binding-like domain superfamily / Zinc finger RING-type profile. / Zinc finger, RING-type / Armadillo-like helical / Armadillo-type fold / Zinc finger, RING/FYVE/PHD-type / Ribosomal protein L2, domain 2 / Winged helix-like DNA-binding domain superfamily
Similarity search - Domain/homology
E3 ubiquitin-protein ligase RBX1 / Cullin-9
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 4.4 Å
AuthorsHopf, L.V.M. / Horn-Ghetko, D. / Schulman, B.A.
Funding supportEuropean Union, Germany, 2items
OrganizationGrant numberCountry
European Research Council (ERC)789016European Union
Max Planck Society Germany
CitationJournal: Nat Struct Mol Biol / Year: 2024
Title: Noncanonical assembly, neddylation and chimeric cullin-RING/RBR ubiquitylation by the 1.8 MDa CUL9 E3 ligase complex.
Authors: Daniel Horn-Ghetko / Linus V M Hopf / Ishita Tripathi-Giesgen / Jiale Du / Sebastian Kostrhon / D Tung Vu / Viola Beier / Barbara Steigenberger / J Rajan Prabu / Luca Stier / Elias M Bruss / ...Authors: Daniel Horn-Ghetko / Linus V M Hopf / Ishita Tripathi-Giesgen / Jiale Du / Sebastian Kostrhon / D Tung Vu / Viola Beier / Barbara Steigenberger / J Rajan Prabu / Luca Stier / Elias M Bruss / Matthias Mann / Yue Xiong / Brenda A Schulman /
Abstract: Ubiquitin ligation is typically executed by hallmark E3 catalytic domains. Two such domains, 'cullin-RING' and 'RBR', are individually found in several hundred human E3 ligases, and collaborate with ...Ubiquitin ligation is typically executed by hallmark E3 catalytic domains. Two such domains, 'cullin-RING' and 'RBR', are individually found in several hundred human E3 ligases, and collaborate with E2 enzymes to catalyze ubiquitylation. However, the vertebrate-specific CUL9 complex with RBX1 (also called ROC1), of interest due to its tumor suppressive interaction with TP53, uniquely encompasses both cullin-RING and RBR domains. Here, cryo-EM, biochemistry and cellular assays elucidate a 1.8-MDa hexameric human CUL9-RBX1 assembly. Within one dimeric subcomplex, an E2-bound RBR domain is activated by neddylation of its own cullin domain and positioning from the adjacent CUL9-RBX1 in trans. Our data show CUL9 as unique among RBX1-bound cullins in dependence on the metazoan-specific UBE2F neddylation enzyme, while the RBR domain protects it from deneddylation. Substrates are recruited to various upstream domains, while ubiquitylation relies on both CUL9's neddylated cullin and RBR domains achieving self-assembled and chimeric cullin-RING/RBR E3 ligase activity.
History
DepositionAug 16, 2023Deposition site: PDBE / Processing site: PDBE
Revision 1.0Apr 17, 2024Provider: repository / Type: Initial release
Revision 1.1Apr 24, 2024Group: Database references / Category: citation / citation_author / Item: _citation.pdbx_database_id_PubMed / _citation.title
Revision 1.2Jul 31, 2024Group: Data collection / Database references / Category: citation / em_admin
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _em_admin.last_update

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Cullin-9
B: Cullin-9
C: E3 ubiquitin-protein ligase RBX1
D: E3 ubiquitin-protein ligase RBX1
E: Cullin-9
F: Cullin-9
G: E3 ubiquitin-protein ligase RBX1
H: E3 ubiquitin-protein ligase RBX1
I: Cullin-9
J: Cullin-9
K: E3 ubiquitin-protein ligase RBX1
L: E3 ubiquitin-protein ligase RBX1


Theoretical massNumber of molelcules
Total (without water)1,762,93112
Polymers1,762,93112
Non-polymers00
Water00
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: gel filtration, not applicable
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1

-
Components

#1: Protein
Cullin-9 / CUL-9 / UbcH7-associated protein 1 / p53-associated parkin-like cytoplasmic protein


Mass: 281531.875 Da / Num. of mol.: 6
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: CUL9, H7AP1, KIAA0708, PARC / Production host: Homo sapiens (human) / References: UniProt: Q8IWT3
#2: Protein
E3 ubiquitin-protein ligase RBX1 / E3 ubiquitin-protein transferase RBX1 / Protein ZYP / RING finger protein 75 / RING-box protein 1 / ...E3 ubiquitin-protein transferase RBX1 / Protein ZYP / RING finger protein 75 / RING-box protein 1 / Rbx1 / Regulator of cullins 1 / ROC1


Mass: 12289.977 Da / Num. of mol.: 6 / Mutation: p.M1_A4del
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: RBX1, RNF75, ROC1 / Production host: Homo sapiens (human)
References: UniProt: P62877, RING-type E3 ubiquitin transferase, cullin-RING-type E3 NEDD8 transferase

-
Experimental details

-
Experiment

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

-
Sample preparation

ComponentName: Structure of CUL9-RBX1 ubiquitin E3 ligase complex - hexameric assembly
Type: COMPLEX / Entity ID: all / Source: RECOMBINANT
Source (natural)Organism: Homo sapiens (human)
Source (recombinant)Organism: Homo sapiens (human)
Buffer solutionpH: 7.5
SpecimenConc.: 3 mg/ml / Embedding 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: 200 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELD / Nominal defocus max: 2800 nm / Nominal defocus min: 700 nm
Image recordingElectron dose: 60 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k)

-
Processing

EM softwareName: PHENIX / Version: 1.17.1_3660: / Category: model refinement
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
3D reconstructionResolution: 4.4 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 611252 / Symmetry type: POINT
Refine LS restraints
Refine-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.00417770
ELECTRON MICROSCOPYf_angle_d0.59324435
ELECTRON MICROSCOPYf_dihedral_angle_d4.6942801
ELECTRON MICROSCOPYf_chiral_restr0.043033
ELECTRON MICROSCOPYf_plane_restr0.0053177

+
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