[English] 日本語
Yorodumi
- PDB-6w66: The structure of the F64A, S172A mutant Keap1-BTB domain in compl... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6w66
TitleThe structure of the F64A, S172A mutant Keap1-BTB domain in complex with SKP1-FBXL17
Components
  • F-box/LRR-repeat protein 17
  • Kelch-like ECH-associated protein 1
  • S-phase kinase-associated protein 1
KeywordsLIGASE/SIGNALING PROTEIN / E3 Ligase / Complex / BTB domain / LIGASE / LIGASE-SIGNALING PROTEIN complex
Function / homology
Function and homology information


F-box domain binding / PcG protein complex / regulation of epidermal cell differentiation / Cul7-RING ubiquitin ligase complex / positive regulation of ubiquitin protein ligase activity / maintenance of protein location in nucleus / Loss of Function of FBXW7 in Cancer and NOTCH1 Signaling / regulation of smoothened signaling pathway / neural crest cell differentiation / SCF-dependent proteasomal ubiquitin-dependent protein catabolic process ...F-box domain binding / PcG protein complex / regulation of epidermal cell differentiation / Cul7-RING ubiquitin ligase complex / positive regulation of ubiquitin protein ligase activity / maintenance of protein location in nucleus / Loss of Function of FBXW7 in Cancer and NOTCH1 Signaling / regulation of smoothened signaling pathway / neural crest cell differentiation / SCF-dependent proteasomal ubiquitin-dependent protein catabolic process / Nuclear events mediated by NFE2L2 / SCF ubiquitin ligase complex / ubiquitin ligase complex scaffold activity / Cul3-RING ubiquitin ligase complex / protein quality control for misfolded or incompletely synthesized proteins / entrainment of circadian clock by photoperiod / Prolactin receptor signaling / protein monoubiquitination / cullin family protein binding / ubiquitin-like ligase-substrate adaptor activity / centriolar satellite / protein K48-linked ubiquitination / Nuclear events stimulated by ALK signaling in cancer / inclusion body / cellular response to interleukin-4 / Regulation of BACH1 activity / MAP3K8 (TPL2)-dependent MAPK1/3 activation / regulation of autophagy / SCF-beta-TrCP mediated degradation of Emi1 / NIK-->noncanonical NF-kB signaling / molecular function activator activity / actin filament / Vpu mediated degradation of CD4 / 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 / 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 / NOTCH1 Intracellular Domain Regulates Transcription / CLEC7A (Dectin-1) signaling / beta-catenin binding / SCF(Skp2)-mediated degradation of p27/p21 / Constitutive Signaling by NOTCH1 PEST Domain Mutants / Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants / FCERI mediated NF-kB activation / Interleukin-1 signaling / protein polyubiquitination / Orc1 removal from chromatin / Regulation of RUNX2 expression and activity / Cyclin D associated events in G1 / disordered domain specific binding / KEAP1-NFE2L2 pathway / Regulation of PLK1 Activity at G2/M Transition / positive regulation of proteasomal ubiquitin-dependent protein catabolic process / Antigen processing: Ubiquitination & Proteasome degradation / Circadian Clock / Downstream TCR signaling / cellular response to oxidative stress / Neddylation / nervous system development / midbody / ubiquitin-dependent protein catabolic process / proteasome-mediated ubiquitin-dependent protein catabolic process / in utero embryonic development / RNA polymerase II-specific DNA-binding transcription factor binding / Potential therapeutics for SARS / protein ubiquitination / Ub-specific processing proteases / chromatin remodeling / protein domain specific binding / centrosome / endoplasmic reticulum / nucleoplasm / identical protein binding / nucleus / 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 / Kelch-like ECH-associated protein 1 / : / F-box domain / BTB-kelch protein / BTB/Kelch-associated / BTB And C-terminal Kelch / BTB And C-terminal Kelch / Leucine Rich repeat / Kelch / Kelch repeat type 1 / Kelch motif / 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
Similarity search - Domain/homology
S-phase kinase-associated protein 1 / Kelch-like ECH-associated protein 1 / F-box/LRR-repeat protein 17
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / molecular replacement / Resolution: 3.21 Å
AuthorsMena, E.L. / Gee, C.L. / 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 16, 2020Deposition site: RCSB / Processing site: RCSB
Revision 1.0Aug 19, 2020Provider: repository / Type: Initial release
Revision 1.1Sep 2, 2020Group: Database references / Category: citation / citation_author
Item: _citation.pdbx_database_id_PubMed / _citation.title / _citation_author.identifier_ORCID
Revision 1.2Oct 28, 2020Group: Database references / Category: citation
Item: _citation.journal_volume / _citation.page_first / _citation.page_last
Revision 1.3Oct 18, 2023Group: Data collection / Database references / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession

-
Structure visualization

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


Theoretical massNumber of molelcules
Total (without water)78,5113
Polymers78,5113
Non-polymers00
Water0
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area6450 Å2
ΔGint-43 kcal/mol
Surface area30930 Å2
MethodPISA
Unit cell
Length a, b, c (Å)183.665, 183.665, 55.370
Angle α, β, γ (deg.)90.000, 90.000, 120.000
Int Tables number154
Space group name H-MP3221
Space group name HallP322"

-
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: Escherichia coli BL21(DE3) (bacteria) / Strain (production host): LOBSTR / 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 / Cell line (production host): High Five / 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: 14861.131 Da / Num. of mol.: 1 / Fragment: BTB domain / Mutation: F64A/S172A
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: KEAP1, INRF2, KIAA0132, KLHL19 / Production host: Escherichia coli BL21(DE3) (bacteria) / Strain (production host): LOBSTR / References: UniProt: Q14145

-
Experimental details

-
Experiment

ExperimentMethod: X-RAY DIFFRACTION / Number of used crystals: 1

-
Sample preparation

CrystalDensity Matthews: 3.43 Å3/Da / Density % sol: 64.16 %
Crystal growTemperature: 291 K / Method: vapor diffusion, hanging drop
Details: well solution 37.5 ul of 50 mM MgCl2, 100 mM HEPES pH 7.5, 30% (v/v) PEG MME 550 (E7 Hampton Index) + 12.5ul H2O mixed 1:1 with complex at 15mg/ml in 150 mM NaCl, 25 mM Tris/HCl pH 8.0

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: ALS / Beamline: 8.3.1 / Wavelength: 1.11583 Å
DetectorType: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Dec 3, 2018
RadiationMonochromator: S111 / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.11583 Å / Relative weight: 1
ReflectionResolution: 3.21→159.06 Å / Num. obs: 17752 / % possible obs: 99.6 % / Redundancy: 10.6 % / Biso Wilson estimate: 101.91 Å2 / CC1/2: 0.998 / Rmerge(I) obs: 0.289 / Rpim(I) all: 0.093 / Rrim(I) all: 0.304 / Net I/σ(I): 7.6
Reflection shell

Diffraction-ID: 1

Resolution (Å)Redundancy (%)Rmerge(I) obsNum. measured allNum. unique obsCC1/2Rpim(I) allRrim(I) allNet I/σ(I) obs% possible all
3.21-3.4310.24.1453201031390.4521.3444.3630.798
9.07-159.06100.033842584610.0110.03552.599.8

-
Phasing

PhasingMethod: molecular replacement
Phasing MR
Highest resolutionLowest resolution
Rotation3.21 Å79.53 Å
Translation3.21 Å79.53 Å

-
Processing

Software
NameVersionClassification
PHENIX1.14_3260refinement
XDSdata reduction
Aimless0.7.3data scaling
PHASER2.8.2phasing
PDB_EXTRACT3.25data extraction
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 4CXI, 2ASS, 1FQV

4cxi

2ass

1fqv


Resolution: 3.21→79.53 Å / SU ML: 0.4835 / Cross valid method: THROUGHOUT / σ(F): 1.34 / Phase error: 37.2992
RfactorNum. reflection% reflection
Rfree0.2896 823 4.7 %
Rwork0.2518 --
obs0.2535 17524 98.44 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å
Displacement parametersBiso mean: 119.12 Å2
Refinement stepCycle: LAST / Resolution: 3.21→79.53 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms5220 0 0 0 5220
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.00165300
X-RAY DIFFRACTIONf_angle_d0.41777155
X-RAY DIFFRACTIONf_chiral_restr0.0385832
X-RAY DIFFRACTIONf_plane_restr0.0026910
X-RAY DIFFRACTIONf_dihedral_angle_d8.3183267
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
3.21-3.410.40841160.40552624X-RAY DIFFRACTION93.32
3.41-3.670.38781500.36472765X-RAY DIFFRACTION99.35
3.67-4.040.36641460.29982759X-RAY DIFFRACTION98.71
4.04-4.630.27451200.2482824X-RAY DIFFRACTION99.59
4.63-5.830.28441480.25022809X-RAY DIFFRACTION99.8
5.83-79.50.23241430.19392920X-RAY DIFFRACTION99.84

+
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