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- PDB-8ubu: Cryo-EM structure of dimeric SCF-FBXL17-BACH1BTB E3 ligase comple... -

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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 / positive regulation of ubiquitin protein ligase activity / cellular response to chemical stress ...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 / positive regulation of ubiquitin protein ligase activity / cellular response to chemical stress / 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 / RNA polymerase II transcription initiation surveillance / protein neddylation / NEDD8 ligase activity / VCB complex / neural crest cell differentiation / negative regulation of response to oxidative stress / Cul5-RING ubiquitin ligase complex / regulation of metabolic process / NFE2L2 regulating anti-oxidant/detoxification enzymes / SCF ubiquitin ligase complex / Cul2-RING ubiquitin ligase complex / negative regulation of type I interferon production / ubiquitin-ubiquitin ligase activity / SCF-dependent proteasomal ubiquitin-dependent protein catabolic process / Cul4A-RING E3 ubiquitin ligase complex / Cul4-RING E3 ubiquitin ligase complex / 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 / transcription-coupled nucleotide-excision repair / regulation of cellular response to insulin stimulus / positive regulation of TORC1 signaling / post-translational protein modification / intrinsic apoptotic signaling pathway / negative regulation of insulin receptor signaling pathway / Regulation of BACH1 activity / T cell activation / 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 / Degradation of DVL / cellular response to amino acid stimulus / Dectin-1 mediated noncanonical NF-kB signaling / Activation of NF-kappaB in B cells / Degradation of GLI1 by the proteasome / Iron uptake and transport / Heme signaling / GSK3B and BTRC:CUL1-mediated-degradation of NFE2L2 / Recognition of DNA damage by PCNA-containing replication complex / Negative regulation of NOTCH4 signaling / Vif-mediated degradation of APOBEC3G / Hedgehog 'on' state / G1/S transition of mitotic cell cycle / Degradation of GLI2 by the proteasome / GLI3 is processed to GLI3R by the proteasome / negative regulation of canonical Wnt signaling pathway / FBXL7 down-regulates AURKA during mitotic entry and in early mitosis / DNA Damage Recognition in GG-NER / Degradation of beta-catenin by the destruction complex / RING-type E3 ubiquitin transferase / beta-catenin binding / Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha / Evasion by RSV of host interferon responses / NOTCH1 Intracellular Domain Regulates Transcription / Dual Incision in GG-NER / Transcription-Coupled Nucleotide Excision Repair (TC-NER) / CLEC7A (Dectin-1) signaling / Formation of TC-NER Pre-Incision Complex / SCF(Skp2)-mediated degradation of p27/p21 / DNA-binding transcription repressor activity, RNA polymerase II-specific / Constitutive Signaling by NOTCH1 PEST Domain Mutants / Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants / FCERI mediated NF-kB activation / Regulation of expression of SLITs and ROBOs / RNA polymerase II transcription regulator complex / Formation of Incision Complex in GG-NER / Interleukin-1 signaling / Orc1 removal from chromatin / protein polyubiquitination / Dual incision in TC-NER / Regulation of RAS by GAPs / Gap-filling DNA repair synthesis and ligation in TC-NER / Regulation of RUNX2 expression and activity
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 / : / A Receptor for Ubiquitination Targets / Leucine-rich repeat, cysteine-containing subtype / Leucine-rich repeat - CC (cysteine-containing) subfamily / 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 / : / A Receptor for Ubiquitination Targets / Leucine-rich repeat, cysteine-containing subtype / Leucine-rich repeat - CC (cysteine-containing) subfamily / F-box domain profile. / F-box-like / F-box-like domain superfamily / 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. / Basic-leucine zipper (bZIP) domain profile. / basic region leucin zipper / Leucine Rich repeat / 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

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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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

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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

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Experimental details

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Experiment

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

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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

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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)

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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

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