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- EMDB-19766: Cryo-EM structure of SKP1-FBXO22 in complex with a BACH1 BTB dime... -

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Basic information

Entry
Database: EMDB / ID: EMD-19766
TitleCryo-EM structure of SKP1-FBXO22 in complex with a BACH1 BTB dimer at 3.2A resolution
Map data
Sample
  • Complex: SKP1-FBXO22-BACH1BTB complex
    • Complex: SKP1-FBXO22
      • Protein or peptide: F-box only protein 22
    • Complex: Transcription regulator protein BACH1
      • Protein or peptide: Transcription regulator protein BACH1
      • Protein or peptide: S-phase kinase-associated protein 1
KeywordsSKP1-FBXO22 E3 ligase SCF F-box protein BACH1 BTB / LIGASE
Function / homology
Function and homology information


regulation of skeletal muscle fiber development / Regulation of HMOX1 expression and activity / F-box domain binding / PcG protein complex / ligand-modulated transcription factor activity / positive regulation of ubiquitin protein ligase activity / Cul7-RING ubiquitin ligase complex / Loss of Function of FBXW7 in Cancer and NOTCH1 Signaling / maintenance of protein location in nucleus / nucleocytoplasmic transport ...regulation of skeletal muscle fiber development / Regulation of HMOX1 expression and activity / F-box domain binding / PcG protein complex / ligand-modulated transcription factor activity / positive regulation of ubiquitin protein ligase activity / Cul7-RING ubiquitin ligase complex / Loss of Function of FBXW7 in Cancer and NOTCH1 Signaling / maintenance of protein location in nucleus / nucleocytoplasmic transport / regulation of metabolic process / SCF ubiquitin ligase complex / NFE2L2 regulating anti-oxidant/detoxification enzymes / SCF-dependent proteasomal ubiquitin-dependent protein catabolic process / ubiquitin ligase complex scaffold activity / Prolactin receptor signaling / 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 BACH1 activity / molecular function activator activity / MAP3K8 (TPL2)-dependent MAPK1/3 activation / cellular response to starvation / SCF-beta-TrCP mediated degradation of Emi1 / NIK-->noncanonical NF-kB signaling / Vpu mediated degradation of CD4 / Dectin-1 mediated noncanonical NF-kB signaling / Activation of NF-kappaB in B cells / Degradation of GLI1 by the proteasome / Iron uptake and transport / GSK3B and BTRC:CUL1-mediated-degradation of NFE2L2 / Heme signaling / Negative regulation of NOTCH4 signaling / 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 / Degradation of beta-catenin by the destruction complex / beta-catenin binding / protein modification process / NOTCH1 Intracellular Domain Regulates Transcription / CLEC7A (Dectin-1) signaling / 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 / RNA polymerase II transcription regulator complex / Z disc / Interleukin-1 signaling / Orc1 removal from chromatin / protein polyubiquitination / Regulation of RUNX2 expression and activity / ubiquitin-protein transferase activity / Cyclin D associated events in G1 / : / Regulation of PLK1 Activity at G2/M Transition / Downstream TCR signaling / Antigen processing: Ubiquitination & Proteasome degradation / positive regulation of proteasomal ubiquitin-dependent protein catabolic process / Neddylation / DNA-binding transcription activator activity, RNA polymerase II-specific / ubiquitin-dependent protein catabolic process / proteasome-mediated ubiquitin-dependent protein catabolic process / DNA-binding transcription factor activity, RNA polymerase II-specific / protein ubiquitination / RNA polymerase II cis-regulatory region sequence-specific DNA binding / chromatin remodeling / DNA-binding transcription factor activity / protein domain specific binding / DNA repair / heme binding / centrosome / regulation of DNA-templated transcription / regulation of transcription by RNA polymerase II / chromatin / negative regulation of transcription by RNA polymerase II / nucleoplasm / nucleus / cytoplasm / cytosol
Similarity search - Function
FIST, C-domain / FIST C domain / FIST_C / BACH, basic leucine zipper (bZIP) domain / F-box domain / Basic leucine zipper domain, Maf-type / bZIP Maf transcription factor / Transcription factor, Skn-1-like, DNA-binding domain superfamily / : / F-box-like domain superfamily ...FIST, C-domain / FIST C domain / FIST_C / BACH, basic leucine zipper (bZIP) domain / F-box domain / Basic leucine zipper domain, Maf-type / bZIP Maf transcription factor / Transcription factor, Skn-1-like, DNA-binding domain superfamily / : / 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 / Basic-leucine zipper (bZIP) domain signature. / Basic-leucine zipper (bZIP) domain profile. / basic region leucin zipper / Basic-leucine zipper domain / 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
Similarity search - Domain/homology
Transcription regulator protein BACH1 / S-phase kinase-associated protein 1 / F-box only protein 22
Similarity search - Component
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.2 Å
AuthorsKhoshouei M / Goretzki B
Funding support1 items
OrganizationGrant numberCountry
Not funded
CitationJournal: Cell / Year: 2024
Title: Dual BACH1 regulation by complementary SCF-type E3 ligases.
Authors: Benedikt Goretzki / Maryam Khoshouei / Martin Schröder / Patrick Penner / Luca Egger / Christine Stephan / Dayana Argoti / Nele Dierlamm / Jimena Maria Rada / Sandra Kapps / Catrin Swantje ...Authors: Benedikt Goretzki / Maryam Khoshouei / Martin Schröder / Patrick Penner / Luca Egger / Christine Stephan / Dayana Argoti / Nele Dierlamm / Jimena Maria Rada / Sandra Kapps / Catrin Swantje Müller / Zacharias Thiel / Merve Mutlu / Claude Tschopp / David Furkert / Felix Freuler / Simon Haenni / Laurent Tenaillon / Britta Knapp / Alexandra Hinniger / Philipp Hoppe / Enrico Schmidt / Sascha Gutmann / Mario Iurlaro / Grigory Ryzhakov / César Fernández /
Abstract: Broad-complex, tramtrack, and bric-à-brac domain (BTB) and CNC homolog 1 (BACH1) is a key regulator of the cellular oxidative stress response and an oncogene that undergoes tight post-translational ...Broad-complex, tramtrack, and bric-à-brac domain (BTB) and CNC homolog 1 (BACH1) is a key regulator of the cellular oxidative stress response and an oncogene that undergoes tight post-translational control by two distinct F-box ubiquitin ligases, SCF and SCF. However, how both ligases recognize BACH1 under oxidative stress is unclear. In our study, we elucidate the mechanism by which FBXO22 recognizes a quaternary degron in a domain-swapped β-sheet of the BACH1 BTB dimer. Cancer-associated mutations and cysteine modifications destabilize the degron and impair FBXO22 binding but simultaneously expose an otherwise shielded degron in the dimer interface, allowing FBXL17 to recognize BACH1 as a monomer. These findings shed light on a ligase switch mechanism that enables post-translational regulation of BACH1 by complementary ligases depending on the stability of its BTB domain. Our results provide mechanistic insights into the oxidative stress response and may spur therapeutic approaches for targeting oxidative stress-related disorders and cancer.
History
DepositionFeb 29, 2024-
Header (metadata) releaseDec 11, 2024-
Map releaseDec 11, 2024-
UpdateJul 2, 2025-
Current statusJul 2, 2025Processing site: PDBe / Status: Released

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Structure visualization

Supplemental images

emd_19766.png

Downloads & links

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Map

FileDownload / File: emd_19766.map.gz / Format: CCP4 / Size: 30.5 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

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AxesZ (Sec.)Y (Row.)X (Col.)
0.85 Å/pix.
x 200 pix.
= 169. Å		0.85 Å/pix.
x 200 pix.
= 169. Å		0.85 Å/pix.
x 200 pix.
= 169. Å

Surface

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Images are generated by Spider.

Voxel sizeX=Y=Z: 0.845 Å
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Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.441
Minimum - Maximum-5.273945 - 6.425545
Average (Standard dev.)0.000069854344 (±0.122242965)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions200200200
Spacing200200200
CellA=B=C: 169.0 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: #1

Fileemd_19766_half_map_1.map
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Half map: #2

Fileemd_19766_half_map_2.map
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Sample components

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Entire : SKP1-FBXO22-BACH1BTB complex

EntireName: SKP1-FBXO22-BACH1BTB complex
Components
  • Complex: SKP1-FBXO22-BACH1BTB complex
    • Complex: SKP1-FBXO22
      • Protein or peptide: F-box only protein 22
    • Complex: Transcription regulator protein BACH1
      • Protein or peptide: Transcription regulator protein BACH1
      • Protein or peptide: S-phase kinase-associated protein 1

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Supramolecule #1: SKP1-FBXO22-BACH1BTB complex

SupramoleculeName: SKP1-FBXO22-BACH1BTB complex / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all
Molecular weightTheoretical: 62 kDa/nm

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Supramolecule #2: SKP1-FBXO22

SupramoleculeName: SKP1-FBXO22 / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #3
Source (natural)Organism: Homo sapiens (human)

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Supramolecule #3: Transcription regulator protein BACH1

SupramoleculeName: Transcription regulator protein BACH1 / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #1-#2
Source (natural)Organism: Homo sapiens (human)

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Macromolecule #1: Transcription regulator protein BACH1

MacromoleculeName: Transcription regulator protein BACH1 / type: protein_or_peptide / ID: 1 / Number of copies: 2 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 14.186162 KDa
Recombinant expressionOrganism: Escherichia coli (E. coli)
SequenceString:
QSMSVFAYES SVHSTNVLLS LNDQRKKDVL CDVTIFVEGQ RFRAHRSVLA ACSSYFHSRI VGQADGELNI TLPEEVTVKG FEPLIQFAY TAKLILSKEN VDEVCKCVEF LSVHNIEESC FQFLKF

UniProtKB: Transcription regulator protein BACH1

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Macromolecule #2: S-phase kinase-associated protein 1

MacromoleculeName: S-phase kinase-associated protein 1 / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 18.679965 KDa
Recombinant expressionOrganism: Spodoptera frugiperda (fall armyworm)
SequenceString:
MPSIKLQSSD GEIFEVDVEI AKQSVTIKTM LEDLGMDDEG DDDPVPLPNV NAAILKKVIQ WCTHHKDDPP PPEDDENKEK RTDDIPVWD QEFLKVDQGT LFELILAANY LDIKGLLDVT CKTVANMIKG KTPEEIRKTF NIKNDFTEEE EAQVRKENQW C EEK

UniProtKB: S-phase kinase-associated protein 1

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Macromolecule #3: F-box only protein 22

MacromoleculeName: F-box only protein 22 / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 43.597062 KDa
Recombinant expressionOrganism: Spodoptera frugiperda (fall armyworm)
SequenceString: GGSGSSVDPR STFVLSNLAE VVERVLTFLP AKALLRVACV CRLWRECVRR VLRTHRSVTW ISAGLAEAGH LEGHCLVRVV AEELENVRI LPHTVLYMAD SETFISLEEC RGHKRARKRT SMETALALEK LFPKQCQVLG IVTPGIVVTP MGSGSNRPQE I EIGESGFA ...String:
GGSGSSVDPR STFVLSNLAE VVERVLTFLP AKALLRVACV CRLWRECVRR VLRTHRSVTW ISAGLAEAGH LEGHCLVRVV AEELENVRI LPHTVLYMAD SETFISLEEC RGHKRARKRT SMETALALEK LFPKQCQVLG IVTPGIVVTP MGSGSNRPQE I EIGESGFA LLFPQIEGIK IQPFHFIKDP KNLTLERHQL TEVGLLDNPE LRVVLVFGYN CCKVGASNYL QQVVSTFSDM NI ILAGGQV DNLSSLTSEK NPLDIDASGV VGLSFSGHRI QSATVLLNED VSDEKTAEAA MQRLKAANIP EHNTIGFMFA CVG RGFQYY RAKGNVEADA FRKFFPSVPL FGFFGNGEIG CDRIVTGNFI LRKCNEVKDD DLFHSYTTIM ALIHLGSSK

UniProtKB: F-box only protein 22

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Experimental details

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Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

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Sample preparation

Concentration20 mg/mL
BufferpH: 7.5
VitrificationCryogen name: ETHANE

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Electron microscopy

MicroscopeFEI TITAN KRIOS
Image recordingFilm or detector model: FEI FALCON IV (4k x 4k) / Average electron dose: 50.0 e/Å2
Details: THERMO SCIENTIFIC FALCON 4i (4k x 4k) direct detector
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 1.6 µm / Nominal defocus min: 0.6 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

CTF correctionType: NONE
Startup modelType of model: INSILICO MODEL
Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.2 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 1715031
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD

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