[English] 日本語
Yorodumi
- PDB-8ubu: Cryo-EM structure of dimeric SCF-FBXL17-BACH1BTB E3 ligase comple... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8ubu
TitleCryo-EM structure of dimeric SCF-FBXL17-BACH1BTB E3 ligase complex close conformation
Components
  • Cullin-1
  • E3 ubiquitin-protein ligase RBX1, N-terminally processed
  • F-box/LRR-repeat protein 17
  • S-phase kinase-associated protein 1
  • Transcription regulator protein BACH1
KeywordsLIGASE / SCF / FBXL17 / BACH1 / F-box protein / CUL1 / Cullin / E3 ligase
Function / homology
Function and homology information


Regulation of HMOX1 expression and activity / Parkin-FBXW7-Cul1 ubiquitin ligase complex / F-box domain binding / PcG protein complex / ligand-modulated transcription factor activity / cullin-RING-type E3 NEDD8 transferase / NEDD8 transferase activity / cullin-RING ubiquitin ligase complex / cellular response to chemical stress / positive regulation of ubiquitin protein ligase activity ...Regulation of HMOX1 expression and activity / Parkin-FBXW7-Cul1 ubiquitin ligase complex / F-box domain binding / PcG protein complex / ligand-modulated transcription factor activity / cullin-RING-type E3 NEDD8 transferase / NEDD8 transferase activity / cullin-RING ubiquitin ligase complex / cellular response to chemical stress / positive regulation of ubiquitin protein ligase activity / Cul7-RING ubiquitin ligase complex / ubiquitin-dependent protein catabolic process via the C-end degron rule pathway / maintenance of protein location in nucleus / Loss of Function of FBXW7 in Cancer and NOTCH1 Signaling / regulation of smoothened signaling pathway / positive regulation of protein autoubiquitination / protein neddylation / NEDD8 ligase activity / negative regulation of response to oxidative stress / regulation of metabolic process / neural crest cell differentiation / Cul5-RING ubiquitin ligase complex / SCF ubiquitin ligase complex / NFE2L2 regulating anti-oxidant/detoxification enzymes / Cul2-RING ubiquitin ligase complex / Cul4A-RING E3 ubiquitin ligase complex / ubiquitin-ubiquitin ligase activity / negative regulation of type I interferon production / SCF-dependent proteasomal ubiquitin-dependent protein catabolic process / Cul3-RING ubiquitin ligase complex / Cul4B-RING E3 ubiquitin ligase complex / ubiquitin ligase complex scaffold activity / negative regulation of mitophagy / Prolactin receptor signaling / protein quality control for misfolded or incompletely synthesized proteins / cullin family protein binding / protein monoubiquitination / ubiquitin-like ligase-substrate adaptor activity / protein K48-linked ubiquitination / Nuclear events stimulated by ALK signaling in cancer / regulation of cellular response to insulin stimulus / positive regulation of TORC1 signaling / negative regulation of insulin receptor signaling pathway / post-translational protein modification / intrinsic apoptotic signaling pathway / T cell activation / Regulation of BACH1 activity / MAP3K8 (TPL2)-dependent MAPK1/3 activation / molecular function activator activity / animal organ morphogenesis / SCF-beta-TrCP mediated degradation of Emi1 / NIK-->noncanonical NF-kB signaling / Vpu mediated degradation of CD4 / cellular response to amino acid stimulus / Degradation of DVL / Dectin-1 mediated noncanonical NF-kB signaling / Activation of NF-kappaB in B cells / Degradation of GLI1 by the proteasome / Recognition of DNA damage by PCNA-containing replication complex / GSK3B and BTRC:CUL1-mediated-degradation of NFE2L2 / Heme signaling / negative regulation of canonical Wnt signaling pathway / Iron uptake and transport / Negative regulation of NOTCH4 signaling / Vif-mediated degradation of APOBEC3G / Hedgehog 'on' state / Degradation of GLI2 by the proteasome / GLI3 is processed to GLI3R by the proteasome / FBXL7 down-regulates AURKA during mitotic entry and in early mitosis / DNA Damage Recognition in GG-NER / RING-type E3 ubiquitin transferase / beta-catenin binding / Degradation of beta-catenin by the destruction complex / Evasion by RSV of host interferon responses / Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha / Dual Incision in GG-NER / Transcription-Coupled Nucleotide Excision Repair (TC-NER) / NOTCH1 Intracellular Domain Regulates Transcription / Formation of TC-NER Pre-Incision Complex / DNA-binding transcription repressor activity, RNA polymerase II-specific / CLEC7A (Dectin-1) signaling / SCF(Skp2)-mediated degradation of p27/p21 / Constitutive Signaling by NOTCH1 PEST Domain Mutants / Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants / G1/S transition of mitotic cell cycle / RNA polymerase II transcription regulator complex / Regulation of expression of SLITs and ROBOs / FCERI mediated NF-kB activation / Formation of Incision Complex in GG-NER / Interleukin-1 signaling / Orc1 removal from chromatin / Dual incision in TC-NER / Regulation of RAS by GAPs / protein polyubiquitination / positive regulation of protein catabolic process / Gap-filling DNA repair synthesis and ligation in TC-NER / Regulation of RUNX2 expression and activity / Cyclin D associated events in G1 / cellular response to UV / KEAP1-NFE2L2 pathway
Similarity search - Function
: / BACH, basic leucine zipper (bZIP) domain / Basic leucine zipper domain, Maf-type / bZIP Maf transcription factor / Transcription factor, Skn-1-like, DNA-binding domain superfamily / : / Leucine-rich repeat, cysteine-containing subtype / Leucine-rich repeat - CC (cysteine-containing) subfamily / A Receptor for Ubiquitination Targets / F-box domain profile. ...: / BACH, basic leucine zipper (bZIP) domain / Basic leucine zipper domain, Maf-type / bZIP Maf transcription factor / Transcription factor, Skn-1-like, DNA-binding domain superfamily / : / Leucine-rich repeat, cysteine-containing subtype / Leucine-rich repeat - CC (cysteine-containing) subfamily / A Receptor for Ubiquitination Targets / F-box domain profile. / F-box-like domain superfamily / F-box-like / SKP1 component, dimerisation / S-phase kinase-associated protein 1 / SKP1-like, dimerisation domain superfamily / Skp1 family, dimerisation domain / F-box domain / Zinc finger, RING-H2-type / RING-H2 zinc finger domain / Cullin protein neddylation domain / : / Cullin, conserved site / Cullin family signature. / Cullin repeat-like-containing domain superfamily / Cullin protein, neddylation domain / Cullin / Cullin protein neddylation domain / Basic-leucine zipper (bZIP) domain signature. / Leucine Rich repeat / Basic-leucine zipper (bZIP) domain profile. / basic region leucin zipper / Cullin / Basic-leucine zipper domain / Cullin, N-terminal / Cullin homology domain / Cullin homology domain superfamily / Cullin family / Cullin family profile. / Basic-leucine zipper domain superfamily / S-phase kinase-associated protein 1-like / SKP1 component, POZ domain / Skp1 family, tetramerisation domain / Found in Skp1 protein family / BTB/POZ domain / BTB domain profile. / Broad-Complex, Tramtrack and Bric a brac / BTB/POZ domain / SKP1/BTB/POZ domain superfamily / Leucine-rich repeat / Leucine-rich repeat domain superfamily / Zinc finger RING-type profile. / Zinc finger, RING-type / Zinc finger, RING/FYVE/PHD-type / Winged helix DNA-binding domain superfamily / Winged helix-like DNA-binding domain superfamily
Similarity search - Domain/homology
Transcription regulator protein BACH1 / E3 ubiquitin-protein ligase RBX1 / S-phase kinase-associated protein 1 / Cullin-1 / F-box/LRR-repeat protein 17
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 4.6 Å
AuthorsShi, H. / Cao, S. / Zheng, N.
Funding support United States, 1items
OrganizationGrant numberCountry
Howard Hughes Medical Institute (HHMI) United States
CitationJournal: Cell / Year: 2024
Title: Recognition of BACH1 quaternary structure degrons by two F-box proteins under oxidative stress.
Authors: Shiyun Cao / Sheena Faye Garcia / Huigang Shi / Ellie I James / Yuki Kito / Hui Shi / Haibin Mao / Sharon Kaisari / Gergely Rona / Sophia Deng / Hailey V Goldberg / Jackeline Ponce / Beatrix ...Authors: Shiyun Cao / Sheena Faye Garcia / Huigang Shi / Ellie I James / Yuki Kito / Hui Shi / Haibin Mao / Sharon Kaisari / Gergely Rona / Sophia Deng / Hailey V Goldberg / Jackeline Ponce / Beatrix Ueberheide / Luca Lignitto / Miklos Guttman / Michele Pagano / Ning Zheng /
Abstract: Ubiquitin-dependent proteolysis regulates diverse cellular functions with high substrate specificity, which hinges on the ability of ubiquitin E3 ligases to decode the targets' degradation signals, i. ...Ubiquitin-dependent proteolysis regulates diverse cellular functions with high substrate specificity, which hinges on the ability of ubiquitin E3 ligases to decode the targets' degradation signals, i.e., degrons. Here, we show that BACH1, a transcription repressor of antioxidant response genes, features two distinct unconventional degrons encrypted in the quaternary structure of its homodimeric BTB domain. These two degrons are both functionalized by oxidative stress and are deciphered by two complementary E3s. FBXO22 recognizes a degron constructed by the BACH1 BTB domain dimer interface, which is unmasked from transcriptional co-repressors after oxidative stress releases BACH1 from chromatin. When this degron is impaired by oxidation, a second BACH1 degron manifested by its destabilized BTB dimer is probed by a pair of FBXL17 proteins that remodels the substrate into E3-bound monomers for ubiquitination. Our findings highlight the multidimensionality of protein degradation signals and the functional complementarity of different ubiquitin ligases targeting the same substrate.
History
DepositionSep 25, 2023Deposition site: RCSB / Processing site: RCSB
Revision 1.0Nov 6, 2024Provider: repository / Type: Initial release
Revision 1.1Nov 13, 2024Group: Data collection / Database references / Category: citation / citation_author / em_admin
Item: _citation.journal_abbrev / _citation.journal_id_ASTM ..._citation.journal_abbrev / _citation.journal_id_ASTM / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _em_admin.last_update
Revision 1.2Nov 20, 2024Group: Data collection / Database references / Category: citation / em_admin
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_ASTM / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.pdbx_database_id_PubMed / _citation.title / _em_admin.last_update
Revision 1.3Nov 27, 2024Group: Data collection / Category: em_admin / Item: _em_admin.last_update
Revision 1.4Jan 8, 2025Group: 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-1
B: E3 ubiquitin-protein ligase RBX1, N-terminally processed
C: S-phase kinase-associated protein 1
D: F-box/LRR-repeat protein 17
E: Transcription regulator protein BACH1
G: S-phase kinase-associated protein 1
H: Cullin-1
I: E3 ubiquitin-protein ligase RBX1, N-terminally processed
K: F-box/LRR-repeat protein 17
L: Transcription regulator protein BACH1


Theoretical massNumber of molelcules
Total (without water)352,53710
Polymers352,53710
Non-polymers00
Water00
1


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

-
Components

#1: Protein Cullin-1 / CUL-1


Mass: 88501.945 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: CUL1 / Production host: Escherichia coli BL21 (bacteria) / References: UniProt: Q13616
#2: Protein E3 ubiquitin-protein ligase RBX1, N-terminally processed / E3 ubiquitin-protein transferase RBX1 / N-terminally processed


Mass: 10840.410 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: RBX1, RNF75, ROC1 / Production host: Escherichia coli BL21 (bacteria) / References: UniProt: P62877
#3: Protein S-phase kinase-associated protein 1 / Cyclin-A/CDK2-associated protein p19 / p19A / Organ of Corti protein 2 / OCP-2 / Organ of Corti ...Cyclin-A/CDK2-associated protein p19 / p19A / Organ of Corti protein 2 / OCP-2 / Organ of Corti protein II / OCP-II / RNA polymerase II elongation factor-like protein / SIII / Transcription elongation factor B polypeptide 1-like / p19skp1


Mass: 18580.834 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: SKP1, EMC19, OCP2, SKP1A, TCEB1L / Cell line (production host): High Five / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: P63208
#4: Protein F-box/LRR-repeat protein 17


Mass: 44505.512 Da / Num. of mol.: 2 / Fragment: UNP residues 310-701
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: FBXL17 / Cell line (production host): High Five / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: Q9UF56
#5: Protein Transcription regulator protein BACH1


Mass: 13839.761 Da / Num. of mol.: 2 / Fragment: BTB domain (UNP residues 7-128)
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: BACH1 / Production host: Escherichia coli BL21 (bacteria) / References: UniProt: O14867
Has ligand of interestN
Has protein modificationY

-
Experimental details

-
Experiment

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

-
Sample preparation

ComponentName: The SCF-F-box protein with BACH1 BTB Domain, dimeric SCF-BFXL17-BACH1BTB
Type: COMPLEX / Entity ID: #5, #3-#4, #1-#2 / Source: MULTIPLE SOURCES
Source (natural)Organism: Homo sapiens (human)
Source (recombinant)Organism: Trichoplusia ni (cabbage looper)
Buffer solutionpH: 7.5
SpecimenEmbedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
Specimen supportGrid material: COPPER / Grid mesh size: 300 divisions/in. / Grid type: Quantifoil R1.2/1.3
VitrificationInstrument: FEI VITROBOT MARK IV / Cryogen 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: BRIGHT FIELD / Nominal defocus max: 25000 nm / Nominal defocus min: 5000 nm / Alignment procedure: COMA FREE
Specimen holderCryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER
Image recordingElectron dose: 60 e/Å2 / Film or detector model: FEI FALCON IV (4k x 4k)

-
Processing

EM software
IDNameCategory
2SerialEMimage acquisition
7UCSF Chimeramodel fitting
8PHENIXmodel fitting
10cryoSPARCinitial Euler assignment
11cryoSPARCfinal Euler assignment
12cryoSPARCclassification
13cryoSPARC3D reconstruction
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
3D reconstructionResolution: 4.6 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 71155 / Algorithm: BACK PROJECTION / Symmetry type: POINT
Atomic model buildingProtocol: RIGID BODY FIT / Space: REAL
Atomic model building
IDPDB-ID 3D fitting-IDAccession codeInitial refinement model-IDSource nameType
16WCQ

6wcq

16WCQ1PDBexperimental model
21LDJ

1ldj

11LDJ2PDBexperimental model

+
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