[English] 日本語
Yorodumi
- EMDB-34199: Cryo-EM Structure of the KBTBD2-CUL3-Rbx1 dimeric complex -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-34199
TitleCryo-EM Structure of the KBTBD2-CUL3-Rbx1 dimeric complex
Map data
Sample
  • Complex: KBTBD2-CUL3-Rbx1 dimeric complex
    • Protein or peptide: Kelch repeat and BTB domain-containing protein 2
    • Protein or peptide: E3 ubiquitin-protein ligase RBX1
    • Protein or peptide: Cullin-3
  • Ligand: ZINC ION
Keywordsligase / complex
Function / homology
Function and homology information


positive regulation of mitotic cell cycle phase transition / trophectodermal cellular morphogenesis / liver morphogenesis / POZ domain binding / nuclear protein quality control by the ubiquitin-proteasome system / regulation protein catabolic process at postsynapse / polar microtubule / anaphase-promoting complex-dependent catabolic process / COPII vesicle coating / stem cell division ...positive regulation of mitotic cell cycle phase transition / trophectodermal cellular morphogenesis / liver morphogenesis / POZ domain binding / nuclear protein quality control by the ubiquitin-proteasome system / regulation protein catabolic process at postsynapse / polar microtubule / anaphase-promoting complex-dependent catabolic process / COPII vesicle coating / stem cell division / cullin-RING-type E3 NEDD8 transferase / RHOBTB3 ATPase cycle / NEDD8 transferase activity / cullin-RING ubiquitin ligase complex / embryonic cleavage / cell projection organization / positive regulation of mitotic metaphase/anaphase transition / cellular response to chemical stress / Cul7-RING ubiquitin ligase complex / ubiquitin-dependent protein catabolic process via the C-end degron rule pathway / Loss of Function of FBXW7 in Cancer and NOTCH1 Signaling / positive regulation of protein autoubiquitination / protein neddylation / fibroblast apoptotic process / Notch binding / NEDD8 ligase activity / RHOBTB1 GTPase cycle / Cul5-RING ubiquitin ligase complex / negative regulation of response to oxidative stress / ubiquitin-ubiquitin ligase activity / negative regulation of Rho protein signal transduction / SCF ubiquitin ligase complex / Cul2-RING ubiquitin ligase complex / Cul4A-RING E3 ubiquitin ligase complex / mitotic metaphase chromosome alignment / SCF-dependent proteasomal ubiquitin-dependent protein catabolic process / Cul4B-RING E3 ubiquitin ligase complex / negative regulation of type I interferon production / ubiquitin ligase complex scaffold activity / Cul3-RING ubiquitin ligase complex / stress fiber assembly / positive regulation of cytokinesis / Prolactin receptor signaling / protein monoubiquitination / cullin family protein binding / ubiquitin-like ligase-substrate adaptor activity / sperm flagellum / endoplasmic reticulum to Golgi vesicle-mediated transport / RHOBTB2 GTPase cycle / protein autoubiquitination / protein K48-linked ubiquitination / Nuclear events stimulated by ALK signaling in cancer / gastrulation / positive regulation of TORC1 signaling / post-translational protein modification / intrinsic apoptotic signaling pathway / phosphatidylinositol 3-kinase/protein kinase B signal transduction / regulation of cellular response to insulin stimulus / cyclin binding / Regulation of BACH1 activity / T cell activation / positive regulation of protein ubiquitination / integrin-mediated signaling pathway / Degradation of DVL / cellular response to amino acid stimulus / Recognition of DNA damage by PCNA-containing replication complex / Degradation of GLI1 by the proteasome / Negative regulation of NOTCH4 signaling / GSK3B and BTRC:CUL1-mediated-degradation of NFE2L2 / protein destabilization / Vif-mediated degradation of APOBEC3G / Hedgehog 'on' state / response to insulin / 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 / negative regulation of canonical Wnt signaling pathway / Degradation of beta-catenin by the destruction complex / Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha / lipid metabolic process / Transcription-Coupled Nucleotide Excision Repair (TC-NER) / Formation of TC-NER Pre-Incision Complex / Dual Incision in GG-NER / Evasion by RSV of host interferon responses / mitotic spindle / NOTCH1 Intracellular Domain Regulates Transcription / Wnt signaling pathway / Constitutive Signaling by NOTCH1 PEST Domain Mutants / Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants / Regulation of expression of SLITs and ROBOs / spindle pole / Formation of Incision Complex in GG-NER / Interleukin-1 signaling / Dual incision in TC-NER / Gap-filling DNA repair synthesis and ligation in TC-NER / Orc1 removal from chromatin / protein polyubiquitination / Regulation of RAS by GAPs
Similarity search - Function
Kelch repeat and BTB domain-containing protein 2 / : / Zinc finger, RING-H2-type / RING-H2 zinc finger domain / BTB-kelch protein / BTB/Kelch-associated / BTB And C-terminal Kelch / BTB And C-terminal Kelch / Cullin protein neddylation domain / : ...Kelch repeat and BTB domain-containing protein 2 / : / Zinc finger, RING-H2-type / RING-H2 zinc finger domain / BTB-kelch protein / BTB/Kelch-associated / BTB And C-terminal Kelch / BTB And C-terminal Kelch / 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 / 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 / BTB/POZ domain / BTB domain profile. / Broad-Complex, Tramtrack and Bric a brac / BTB/POZ domain / SKP1/BTB/POZ 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
E3 ubiquitin-protein ligase RBX1 / Cullin-3 / Kelch repeat and BTB domain-containing protein 2
Similarity search - Component
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.96 Å
AuthorsSun L / Chen Z / Hu Y / Mao Q
Funding support China, 1 items
OrganizationGrant numberCountry
National Natural Science Foundation of China (NSFC)81900729 China
CitationJournal: Nat Struct Mol Biol / Year: 2024
Title: Dynamic molecular architecture and substrate recruitment of cullin3-RING E3 ligase CRL3.
Authors: Yuxia Hu / Zhao Zhang / Qiyu Mao / Xiang Zhang / Aihua Hao / Yu Xun / Yeda Wang / Lin Han / Wuqiang Zhan / Qianying Liu / Yue Yin / Chao Peng / Eva Marie Y Moresco / Zhenguo Chen / Bruce Beutler / Lei Sun /
Abstract: Phosphatidylinositol 3-kinase α, a heterodimer of catalytic p110α and one of five regulatory subunits, mediates insulin- and insulin like growth factor-signaling and, frequently, oncogenesis. ...Phosphatidylinositol 3-kinase α, a heterodimer of catalytic p110α and one of five regulatory subunits, mediates insulin- and insulin like growth factor-signaling and, frequently, oncogenesis. Cellular levels of the regulatory p85α subunit are tightly controlled by regulated proteasomal degradation. In adipose tissue and growth plates, failure of K48-linked p85α ubiquitination causes diabetes, lipodystrophy and dwarfism in mice, as in humans with SHORT syndrome. Here we elucidated the structures of the key ubiquitin ligase complexes regulating p85α availability. Specificity is provided by the substrate receptor KBTBD2, which recruits p85α to the cullin3-RING E3 ubiquitin ligase (CRL3). CRL3 forms multimers, which disassemble into dimers upon substrate binding (CRL3-p85α) and/or neddylation by the activator NEDD8 (CRL3~N8), leading to p85α ubiquitination and degradation. Deactivation involves dissociation of NEDD8 mediated by the COP9 signalosome and displacement of KBTBD2 by the inhibitor CAND1. The hereby identified structural basis of p85α regulation opens the way to better understanding disturbances of glucose regulation, growth and cancer.
History
DepositionAug 29, 2022-
Header (metadata) releaseSep 6, 2023-
Map releaseSep 6, 2023-
UpdateMar 20, 2024-
Current statusMar 20, 2024Processing site: PDBj / Status: Released

-
Structure visualization

Supplemental images

emd_34199.png

Downloads & links

-
Map

FileDownload / File: emd_34199.map.gz / Format: CCP4 / Size: 216 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
1.33 Å/pix.
x 384 pix.
= 511.488 Å		1.33 Å/pix.
x 384 pix.
= 511.488 Å		1.33 Å/pix.
x 384 pix.
= 511.488 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 1.332 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.001
Minimum - Maximum-0.0016856322 - 1.6915807
Average (Standard dev.)0.00048696966 (±0.014798456)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions384384384
Spacing384384384
CellA=B=C: 511.488 Å
α=β=γ: 90.0 °

-
Supplemental data

-
Half map: #2

Fileemd_34199_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: #1

Fileemd_34199_half_map_2.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Sample components

-
Entire : KBTBD2-CUL3-Rbx1 dimeric complex

EntireName: KBTBD2-CUL3-Rbx1 dimeric complex
Components
  • Complex: KBTBD2-CUL3-Rbx1 dimeric complex
    • Protein or peptide: Kelch repeat and BTB domain-containing protein 2
    • Protein or peptide: E3 ubiquitin-protein ligase RBX1
    • Protein or peptide: Cullin-3
  • Ligand: ZINC ION

-
Supramolecule #1: KBTBD2-CUL3-Rbx1 dimeric complex

SupramoleculeName: KBTBD2-CUL3-Rbx1 dimeric complex / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#3
Source (natural)Organism: Homo sapiens (human)

-
Macromolecule #1: Kelch repeat and BTB domain-containing protein 2

MacromoleculeName: Kelch repeat and BTB domain-containing protein 2 / type: protein_or_peptide / ID: 1 / Number of copies: 2 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 71.403367 KDa
Recombinant expressionOrganism: Spodoptera frugiperda (fall armyworm)
SequenceString: MSTQDERQIN TEYAVSLLEQ LKLFYEQQLF TDIVLIVEGT EFPCHKMVLA TCSSYFRAMF MSGLSESKQT HVHLRNVDAA TLQIIITYA YTGNLAMNDS TVEQLYETAC FLQVEDVLQR CREYLIKKIN AENCVRLLSF ADLFSCEELK QSAKRMVEHK F TAVYHQDA ...String:
MSTQDERQIN TEYAVSLLEQ LKLFYEQQLF TDIVLIVEGT EFPCHKMVLA TCSSYFRAMF MSGLSESKQT HVHLRNVDAA TLQIIITYA YTGNLAMNDS TVEQLYETAC FLQVEDVLQR CREYLIKKIN AENCVRLLSF ADLFSCEELK QSAKRMVEHK F TAVYHQDA FMQLSHDLLI DILSSDNLNV EKEETVREAA MLWLEYNTES RSQYLSSVLS QIRIDALSEV TQRAWFQGLP PN DKSVVVQ GLYKSMPKFF KPRLGMTKEE MMIFIEASSE NPCSLYSSVC YSPQAEKVYK LCSPPADLHK VGTVVTPDND IYI AGGQVP LKNTKTNHSK TSKLQTAFRT VNCFYWFDAQ QNTWFPKTPM LFVRIKPSLV CCEGYIYAIG GDSVGGELNR RTVE RYDTE KDEWTMVSPL PCAWQWSAAV VVHDCIYVMT LNLMYCYFPR SDSWVEMAMR QTSRSFASAA AFGDKIFYIG GLHIA TNSG IRLPSGTVDG SSVTVEIYDV NKNEWKMAAN IPAKRYSDPC VRAVVISNSL CVFMRETHLN ERAKYVTYQY DLELDR WSL RQHISERVLW DLGRDFRCTV GKLYPSCLEE SPWKPPTYLF STDGTEEFEL DGEMVALPPV

UniProtKB: Kelch repeat and BTB domain-containing protein 2

-
Macromolecule #2: E3 ubiquitin-protein ligase RBX1

MacromoleculeName: E3 ubiquitin-protein ligase RBX1 / type: protein_or_peptide / ID: 2 / Number of copies: 2 / Enantiomer: LEVO / EC number: RING-type E3 ubiquitin transferase
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 13.970756 KDa
Recombinant expressionOrganism: Spodoptera frugiperda (fall armyworm)
SequenceString:
HHHHHHENLY FQGMAAAMDV DTPSGTNSGA GKKRFEVKKW NAVALWAWDI VVDNCAICRN HIMDLCIECQ ANQASATSEE CTVAWGVCN HAFHFHCISR WLKTRQVCPL DNREWEFQKY GH

UniProtKB: E3 ubiquitin-protein ligase RBX1

-
Macromolecule #3: Cullin-3

MacromoleculeName: Cullin-3 / type: protein_or_peptide / ID: 3 / Number of copies: 2 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 90.105469 KDa
Recombinant expressionOrganism: Spodoptera frugiperda (fall armyworm)
SequenceString: WSHPQFEKMS NLSKGTGSRK DTKMRIRAFP MTMDEKYVNS IWDLLKNAIQ EIQRKNNSGL SFEELYRNAY TMVLHKHGEK LYTGLREVV TEHLINKVRE DVLNSLNNNF LQTLNQAWND HQTAMVMIRD ILMYMDRVYV QQNNVENVYN LGLIIFRDQV V RYGCIRDH ...String:
WSHPQFEKMS NLSKGTGSRK DTKMRIRAFP MTMDEKYVNS IWDLLKNAIQ EIQRKNNSGL SFEELYRNAY TMVLHKHGEK LYTGLREVV TEHLINKVRE DVLNSLNNNF LQTLNQAWND HQTAMVMIRD ILMYMDRVYV QQNNVENVYN LGLIIFRDQV V RYGCIRDH LRQTLLDMIA RERKGEVVDR GAIRNACQML MILGLEGRSV YEEDFEAPFL EMSAEFFQME SQKFLAENSA SV YIKKVEA RINEEIERVM HCLDKSTEEP IVKVVERELI SKHMKTIVEM ENSGLVHMLK NGKTEDLGCM YKLFSRVPNG LKT MCECMS SYLREQGKAL VSEEGEGKNP VDYIQGLLDL KSRFDRFLLE SFNNDRLFKQ TIAGDFEYFL NLNSRSPEYL SLFI DDKLK KGVKGLTEQE VETILDKAMV LFRFMQEKDV FERYYKQHLA RRLLTNKSVS DDSEKNMISK LKTECGCQFT SKLEG MFRD MSISNTTMDE FRQHLQATGV SLGGVDLTVR VLTTGYWPTQ SATPKCNIPP APRHAFEIFR RFYLAKHSGR QLTLQH HMG SADLNATFYG PVKKEDGSEV GVGGAQVTGS NTRKHILQVS TFQMTILMLF NNREKYTFEE IQQETDIPER ELVRALQ SL ACGKPTQRVL TKEPKSKEIE NGHIFTVNDQ FTSKLHRVKI QTVAAKQGES DPERKETRQK VDDDRKHEIE AAIVRIMK S RKKMQHNVLV AEVTQQLKAR FLPSPVVIKK RIEGLIEREY LARTPEDRKV YTYVA

UniProtKB: Cullin-3

-
Macromolecule #4: ZINC ION

MacromoleculeName: ZINC ION / type: ligand / ID: 4 / Number of copies: 6 / Formula: ZN
Molecular weightTheoretical: 65.409 Da

-
Experimental details

-
Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

-
Sample preparation

BufferpH: 7.8
VitrificationCryogen name: ETHANE

-
Electron microscopy

MicroscopeFEI TITAN KRIOS
Image recordingFilm or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: SUPER-RESOLUTION / Average electron dose: 45.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.2 µm / Nominal defocus min: 1.2 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

-
Image processing

Startup modelType of model: PDB ENTRY
PDB model - PDB ID:

6i2m


Details: 4A0K
Final reconstructionApplied symmetry - Point group: C1 (asymmetric) / Resolution.type: BY AUTHOR / Resolution: 3.96 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: RELION (ver. 3.0) / Number images used: 433329
Initial angle assignmentType: PROJECTION MATCHING
Final angle assignmentType: PROJECTION MATCHING / Software - Name: RELION (ver. 3.0)

+
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