[English] 日本語
Yorodumi
- PDB-6wcq: Structure of a substrate-bound DQC ubiquitin ligase -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6wcq
TitleStructure of a substrate-bound DQC ubiquitin ligase
Components
  • Cullin-1
  • F-box/LRR-repeat protein 17
  • Kelch-like ECH-associated protein 1
  • S-phase kinase-associated protein 1
KeywordsLIGASE / ubiquitin / E3-ligase / multiprotein complex / substrate recognition
Function / homology
Function and homology information


Parkin-FBXW7-Cul1 ubiquitin ligase complex / F-box domain binding / negative regulation of response to oxidative stress / PcG protein complex / regulation of epidermal cell differentiation / cullin-RING ubiquitin ligase complex / Cul7-RING ubiquitin ligase complex / positive regulation of ubiquitin protein ligase activity / Loss of Function of FBXW7 in Cancer and NOTCH1 Signaling / maintenance of protein location in nucleus ...Parkin-FBXW7-Cul1 ubiquitin ligase complex / F-box domain binding / negative regulation of response to oxidative stress / PcG protein complex / regulation of epidermal cell differentiation / cullin-RING ubiquitin ligase complex / Cul7-RING ubiquitin ligase complex / positive regulation of ubiquitin protein ligase activity / Loss of Function of FBXW7 in Cancer and NOTCH1 Signaling / maintenance of protein location in nucleus / regulation of smoothened signaling pathway / neural crest cell differentiation / Nuclear events mediated by NFE2L2 / SCF ubiquitin ligase complex / ubiquitin ligase complex scaffold activity / SCF-dependent proteasomal ubiquitin-dependent protein catabolic process / Cul3-RING ubiquitin ligase complex / protein quality control for misfolded or incompletely synthesized proteins / Prolactin receptor signaling / entrainment of circadian clock by photoperiod / protein monoubiquitination / cullin family protein binding / centriolar satellite / ubiquitin-like ligase-substrate adaptor activity / cellular response to interleukin-4 / Nuclear events stimulated by ALK signaling in cancer / protein K48-linked ubiquitination / inclusion body / Regulation of BACH1 activity / MAP3K8 (TPL2)-dependent MAPK1/3 activation / intrinsic apoptotic signaling pathway / SCF-beta-TrCP mediated degradation of Emi1 / NIK-->noncanonical NF-kB signaling / regulation of autophagy / molecular function activator activity / Vpu mediated degradation of CD4 / actin filament / Dectin-1 mediated noncanonical NF-kB signaling / Degradation of GLI1 by the proteasome / Activation of NF-kappaB in B cells / Negative regulation of NOTCH4 signaling / animal organ morphogenesis / Iron uptake and transport / GSK3B and BTRC:CUL1-mediated-degradation of NFE2L2 / 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 / negative regulation of DNA-binding transcription factor activity / G1/S transition of mitotic cell cycle / NOTCH1 Intracellular Domain Regulates Transcription / CLEC7A (Dectin-1) signaling / SCF(Skp2)-mediated degradation of p27/p21 / beta-catenin binding / Constitutive Signaling by NOTCH1 PEST Domain Mutants / Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants / FCERI mediated NF-kB activation / Interleukin-1 signaling / Orc1 removal from chromatin / protein polyubiquitination / Regulation of RUNX2 expression and activity / Cyclin D associated events in G1 / KEAP1-NFE2L2 pathway / Regulation of PLK1 Activity at G2/M Transition / disordered domain specific binding / Circadian Clock / positive regulation of proteasomal ubiquitin-dependent protein catabolic process / Antigen processing: Ubiquitination & Proteasome degradation / Downstream TCR signaling / protein-macromolecule adaptor activity / nervous system development / Neddylation / mitotic cell cycle / cellular response to oxidative stress / midbody / ubiquitin-dependent protein catabolic process / proteasome-mediated ubiquitin-dependent protein catabolic process / positive regulation of canonical NF-kappaB signal transduction / in utero embryonic development / RNA polymerase II-specific DNA-binding transcription factor binding / cell population proliferation / Potential therapeutics for SARS / Ub-specific processing proteases / protein ubiquitination / chromatin remodeling / protein domain specific binding / centrosome / ubiquitin protein ligase binding / endoplasmic reticulum / nucleoplasm / identical protein binding / nucleus / plasma membrane / cytosol / cytoplasm
Similarity search - Function
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 ...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 / Kelch-like ECH-associated protein 1 / : / BTB-kelch protein / BTB/Kelch-associated / BTB And C-terminal Kelch / BTB And C-terminal Kelch / Cullin protein neddylation domain / Leucine Rich repeat / Cullin, conserved site / Cullin family signature. / Cullin / Cullin repeat-like-containing domain superfamily / Cullin protein, neddylation domain / Cullin protein neddylation domain / Kelch / Kelch repeat type 1 / Kelch motif / Cullin / Cullin, N-terminal / Cullin homology domain / Cullin homology domain superfamily / Cullin family / Cullin family profile. / Kelch-type beta propeller / 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 / Winged helix DNA-binding domain superfamily / Winged helix-like DNA-binding domain superfamily
Similarity search - Domain/homology
S-phase kinase-associated protein 1 / Cullin-1 / Kelch-like ECH-associated protein 1 / F-box/LRR-repeat protein 17
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 8.5 Å
AuthorsMena, E.L. / Jevtic, P. / Greber, B.J. / Gee, C.L. / Lew, B.G. / Akopian, D. / Nogales, E. / Kuriyan, J. / Rape, M.
Funding support United States, 1items
OrganizationGrant numberCountry
Howard Hughes Medical Institute (HHMI) United States
CitationJournal: Nature / Year: 2020
Title: Structural basis for dimerization quality control.
Authors: Elijah L Mena / Predrag Jevtić / Basil J Greber / Christine L Gee / Brandon G Lew / David Akopian / Eva Nogales / John Kuriyan / Michael Rape /
Abstract: Most quality control pathways target misfolded proteins to prevent toxic aggregation and neurodegeneration. Dimerization quality control further improves proteostasis by eliminating complexes of ...Most quality control pathways target misfolded proteins to prevent toxic aggregation and neurodegeneration. Dimerization quality control further improves proteostasis by eliminating complexes of aberrant composition, but how it detects incorrect subunits remains unknown. Here we provide structural insight into target selection by SCF-FBXL17, a dimerization-quality-control E3 ligase that ubiquitylates and helps to degrade inactive heterodimers of BTB proteins while sparing functional homodimers. We find that SCF-FBXL17 disrupts aberrant BTB dimers that fail to stabilize an intermolecular β-sheet around a highly divergent β-strand of the BTB domain. Complex dissociation allows SCF-FBXL17 to wrap around a single BTB domain, resulting in robust ubiquitylation. SCF-FBXL17 therefore probes both shape and complementarity of BTB domains, a mechanism that is well suited to establish quality control of complex composition for recurrent interaction modules.
History
DepositionMar 31, 2020Deposition site: RCSB / Processing site: RCSB
Revision 1.0Aug 19, 2020Provider: repository / Type: Initial release
Revision 1.1Sep 2, 2020Group: Database references / Category: citation / Item: _citation.pdbx_database_id_PubMed / _citation.title
Revision 1.2Oct 28, 2020Group: Database references / Category: citation
Item: _citation.journal_volume / _citation.page_first / _citation.page_last
Revision 1.3Mar 6, 2024Group: Data collection / Database references / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / em_3d_fitting_list / pdbx_initial_refinement_model
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _em_3d_fitting_list.accession_code / _em_3d_fitting_list.initial_refinement_model_id / _em_3d_fitting_list.source_name / _em_3d_fitting_list.type

-
Structure visualization

Movie
  • Deposited structure unit
  • Imaged by Jmol
  • Download
  • Simplified surface model + fitted atomic model
  • EMDB-21617
  • Imaged by Jmol
  • Download
  • Superimposition on EM map
  • EMDB-21617
  • Imaged by UCSF Chimera
  • Download
Movie viewer
Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: S-phase kinase-associated protein 1
B: F-box/LRR-repeat protein 17
C: Kelch-like ECH-associated protein 1
D: Cullin-1


Theoretical massNumber of molelcules
Total (without water)183,7504
Polymers183,7504
Non-polymers00
Water0
1


  • Idetical with deposited unit
  • defined by author
TypeNameSymmetry operationNumber
identity operation1_5551
Buried area7050 Å2
ΔGint-55 kcal/mol
Surface area50560 Å2

-
Components

#1: Protein S-phase kinase-associated protein 1 / / SKP1 / Cyclin-A/CDK2-associated protein p19 / p19A / Organ of Corti protein 2 / OCP-2 / Organ of ...SKP1 / 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: 18679.965 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: SKP1, EMC19, OCP2, SKP1A, TCEB1L / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: P63208
#2: Protein F-box/LRR-repeat protein 17 / F-box and leucine-rich repeat protein 17 / F-box only protein 13


Mass: 44970.043 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: FBXL17, FBL17, FBX13, FBXO13 / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: Q9UF56
#3: Protein Kelch-like ECH-associated protein 1 / Cytosolic inhibitor of Nrf2 / INrf2 / Kelch-like protein 19


Mass: 70173.484 Da / Num. of mol.: 1 / Mutation: V99A
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: KEAP1, INRF2, KIAA0132, KLHL19 / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: Q14145
#4: Protein Cullin-1 / / CUL-1


Mass: 49926.520 Da / Num. of mol.: 1 / Fragment: residues 1-434
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: CUL1 / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: Q13616

-
Experimental details

-
Experiment

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

-
Sample preparation

ComponentName: CUL1-SKP1-FBXL17-KEAP1 complex / Type: COMPLEX / Entity ID: all / Source: RECOMBINANT
Molecular weightExperimental value: NO
Source (natural)Organism: Homo sapiens (human)
Source (recombinant)Organism: Trichoplusia ni (cabbage looper)
Buffer solution
IDSpecimen-IDpH
118
228
Buffer component
IDConc.NameFormulaBuffer-ID
1150 mMsodium chlorideNaClSodium chloride1
220 mMHEPES-NaOH1
31 mMDTT1
4150 mMSodium chlorideNaClSodium chloride2
520 mMHEPES-NaOH2
61 mMDTT2
Specimen
IDExperiment-IDEmbedding appliedShadowing appliedStaining appliedVitrification appliedDetails
11NONONOYESCrosslinked with BS3
21NONONOYESCrosslinked with BS3
Specimen support
IDSpecimen-IDDetailsGrid materialGrid mesh size (divisions/in.)Grid type
11Glow discharge before deposition of graphene oxide.GOLD300Quantifoil, UltrAuFoil, R1.2/1.3
22A thin carbon film was floated onto the grids, which were glow discharged after drying.COPPERQuantifoil R2/2
Vitrification
IDInstrumentCryogen nameHumidity (%)Specimen-IDChamber temperature (K)Entry-ID
1FEI VITROBOT MARK IVETHANE-PROPANE10012776WCQ
2FEI VITROBOT MARK IVETHANE-PROPANE10022776WCQ

-
Electron microscopy imaging

Experimental equipment
Model: Talos Arctica / Image courtesy: FEI Company
EM imaging

Accelerating voltage: 200 kV / Alignment procedure: COMA FREE / C2 aperture diameter: 50 µm / Cryogen: NITROGEN / Electron source: FIELD EMISSION GUN / Illumination mode: FLOOD BEAM / Model: FEI TALOS ARCTICA / Mode: BRIGHT FIELDBright-field microscopy / Cs: 2.7 mm / Nominal defocus max: 3000 nm / Specimen holder model: OTHER

IDNominal defocus min (nm)Specimen-ID
120001
215002
Image recording
IDImaging-IDElectron dose (e/Å2)Film or detector modelNum. of grids imagedDetector mode
1160GATAN K3 (6k x 4k)1
2250GATAN K2 SUMMIT (4k x 4k)1SUPER-RESOLUTION

-
Processing

SoftwareName: PHENIX / Version: 1.16_3549: / Classification: refinement
EM software
IDNameVersionCategoryImaging-IDDetails
2SerialEMimage acquisition1
4CTFFIND4CTF correction
5GctfCTF correction
8UCSF Chimeramodel fittingFIT IN MAP
10SerialEMimage acquisition2
11RELION3initial Euler assignment
12cryoSPARCinitial Euler assignment
13RELION3final Euler assignment
15RELION33D reconstruction
16PHENIXmodel refinementREAL SPACE REFINE
Image processingDetails: Datasets from K3 and K2 were joined for the final reconstruction.
CTF correctionDetails: As implemented in RELION. / Type: PHASE FLIPPING AND AMPLITUDE CORRECTION
Particle selectionNum. of particles selected: 824561
Details: Total number of particles for both datasets. Selected using RELION auto-picking (Laplacian-of-Gaussian).
SymmetryPoint symmetry: C1 (asymmetric)
3D reconstructionResolution: 8.5 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 160256 / Algorithm: FOURIER SPACE / Num. of class averages: 2 / Symmetry type: POINT
Atomic model buildingProtocol: OTHER / Space: REAL
Details: Coordinates were fitted as rigid bodies or fragments in Chimera and subsequently geometry-optimized using PHENIX real space refinement.
Atomic model building
IDPDB-ID 3D fitting-IDAccession codeInitial refinement model-IDSource nameType
11LDK

1ldk

11LDK1PDBexperimental model
21X1X

1x1x

11X1X2PDBexperimental model
Refine LS restraints
Refine-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.0028266
ELECTRON MICROSCOPYf_angle_d0.56211147
ELECTRON MICROSCOPYf_dihedral_angle_d11.8075061
ELECTRON MICROSCOPYf_chiral_restr0.0381273
ELECTRON MICROSCOPYf_plane_restr0.0031423

+
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