[English] 日本語
Yorodumi
- PDB-8wdk: The complex structure of Cul2-VCB-Protac-Wee1 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8wdk
TitleThe complex structure of Cul2-VCB-Protac-Wee1
Components
  • Cullin-2
  • E3 ubiquitin-protein ligase RBX1, N-terminally processed
  • Elongin-B
  • Elongin-C
  • Wee1-like protein kinase
  • von Hippel-Lindau disease tumor suppressor
KeywordsLIGASE / E3 ligase complex
Function / homology
Function and homology information


G2/M DNA replication checkpoint / negative regulation of G2/M transition of mitotic cell cycle / regulation of cellular response to hypoxia / cullin-RING-type E3 NEDD8 transferase / NEDD8 transferase activity / cullin-RING ubiquitin ligase complex / negative regulation of receptor signaling pathway via JAK-STAT / RHOBTB3 ATPase cycle / Cul7-RING ubiquitin ligase complex / ubiquitin-dependent protein catabolic process via the C-end degron rule pathway ...G2/M DNA replication checkpoint / negative regulation of G2/M transition of mitotic cell cycle / regulation of cellular response to hypoxia / cullin-RING-type E3 NEDD8 transferase / NEDD8 transferase activity / cullin-RING ubiquitin ligase complex / negative regulation of receptor signaling pathway via JAK-STAT / RHOBTB3 ATPase cycle / Cul7-RING ubiquitin ligase complex / ubiquitin-dependent protein catabolic process via the C-end degron rule pathway / cellular response to chemical stress / Loss of Function of FBXW7 in Cancer and NOTCH1 Signaling / transcription elongation factor activity / target-directed miRNA degradation / Polo-like kinase mediated events / elongin complex / positive regulation of protein autoubiquitination / RNA polymerase II transcription initiation surveillance / protein neddylation / Replication of the SARS-CoV-1 genome / NEDD8 ligase activity / negative regulation of response to oxidative stress / VCB complex / Cul5-RING ubiquitin ligase complex / SCF ubiquitin ligase complex / negative regulation of type I interferon production / ubiquitin-ubiquitin ligase activity / intracellular membraneless organelle / SCF-dependent proteasomal ubiquitin-dependent protein catabolic process / Cul2-RING ubiquitin ligase complex / Cul3-RING ubiquitin ligase complex / negative regulation of G1/S transition of mitotic cell cycle / Cul4A-RING E3 ubiquitin ligase complex / Cul4-RING E3 ubiquitin ligase complex / SUMOylation of ubiquitinylation proteins / negative regulation of mitophagy / Prolactin receptor signaling / Cul4B-RING E3 ubiquitin ligase complex / ubiquitin ligase complex scaffold activity / establishment of cell polarity / cullin family protein binding / negative regulation of transcription elongation by RNA polymerase II / Pausing and recovery of Tat-mediated HIV elongation / Tat-mediated HIV elongation arrest and recovery / HIV elongation arrest and recovery / Pausing and recovery of HIV elongation / protein monoubiquitination / negative regulation of signal transduction / Tat-mediated elongation of the HIV-1 transcript / Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex / Formation of HIV-1 elongation complex containing HIV-1 Tat / ubiquitin-like ligase-substrate adaptor activity / protein K48-linked ubiquitination / Cyclin E associated events during G1/S transition / Formation of HIV elongation complex in the absence of HIV Tat / Cyclin A:Cdk2-associated events at S phase entry / Cyclin A/B1/B2 associated events during G2/M transition / Nuclear events stimulated by ALK signaling in cancer / RNA Polymerase II Transcription Elongation / neuron projection morphogenesis / Formation of RNA Pol II elongation complex / negative regulation of TORC1 signaling / transcription-coupled nucleotide-excision repair / RNA Polymerase II Pre-transcription Events / positive regulation of TORC1 signaling / regulation of cellular response to insulin stimulus / negative regulation of insulin receptor signaling pathway / intrinsic apoptotic signaling pathway / protein serine/threonine kinase binding / negative regulation of autophagy / post-translational protein modification / T cell activation / Regulation of BACH1 activity / positive regulation of DNA replication / transcription corepressor binding / non-membrane spanning protein tyrosine kinase activity / TP53 Regulates Transcription of DNA Repair Genes / cellular response to amino acid stimulus / non-specific protein-tyrosine kinase / positive regulation of cell differentiation / transcription initiation at RNA polymerase II promoter / Degradation of DVL / transcription elongation by RNA polymerase II / Degradation of GLI1 by the proteasome / GSK3B and BTRC:CUL1-mediated-degradation of NFE2L2 / Negative regulation of NOTCH4 signaling / G1/S transition of mitotic cell cycle / Recognition of DNA damage by PCNA-containing replication complex / negative regulation of canonical Wnt signaling pathway / Hedgehog 'on' state / Vif-mediated degradation of APOBEC3G / FBXL7 down-regulates AURKA during mitotic entry and in early mitosis / Degradation of GLI2 by the proteasome / GLI3 is processed to GLI3R by the proteasome / RING-type E3 ubiquitin transferase / Inactivation of CSF3 (G-CSF) signaling / Degradation of beta-catenin by the destruction complex / DNA Damage Recognition in GG-NER / Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha / Evasion by RSV of host interferon responses
Similarity search - Function
Wee1-like protein kinase / : / von Hippel-Lindau disease tumour suppressor, beta/alpha domain / von Hippel-Lindau disease tumour suppressor, alpha domain / von Hippel-Lindau disease tumour suppressor, beta domain / VHL superfamily / von Hippel-Lindau disease tumour suppressor, alpha domain superfamily / von Hippel-Lindau disease tumour suppressor, beta domain superfamily / VHL beta domain / VHL box domain ...Wee1-like protein kinase / : / von Hippel-Lindau disease tumour suppressor, beta/alpha domain / von Hippel-Lindau disease tumour suppressor, alpha domain / von Hippel-Lindau disease tumour suppressor, beta domain / VHL superfamily / von Hippel-Lindau disease tumour suppressor, alpha domain superfamily / von Hippel-Lindau disease tumour suppressor, beta domain superfamily / VHL beta domain / VHL 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 / Elongin-C / Elongin B / Cullin / Cullin, N-terminal / Cullin homology domain / Cullin homology domain superfamily / Cullin alpha solenoid domain / Cullin family profile. / S-phase kinase-associated protein 1-like / SKP1 component, POZ domain / Skp1 family, tetramerisation domain / Found in Skp1 protein family / SKP1/BTB/POZ domain superfamily / Zinc finger RING-type profile. / Zinc finger, RING-type / Ubiquitin family / Ubiquitin homologues / Ubiquitin domain profile. / Ubiquitin-like domain / Zinc finger, RING/FYVE/PHD-type / Ubiquitin-like domain superfamily / Winged helix DNA-binding domain superfamily / Serine/threonine-protein kinase, active site / Serine/Threonine protein kinases active-site signature. / Protein kinase domain / Winged helix-like DNA-binding domain superfamily / Serine/Threonine protein kinases, catalytic domain / Protein kinase, ATP binding site / Protein kinases ATP-binding region signature. / Protein kinase domain profile. / Protein kinase domain / Protein kinase-like domain superfamily
Similarity search - Domain/homology
: / Wee1-like protein kinase / von Hippel-Lindau disease tumor suppressor / E3 ubiquitin-protein ligase RBX1 / Cullin-2 / Elongin-C / Elongin-B
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.64 Å
AuthorsWang, P. / Zhang, T.T.
Funding support1items
OrganizationGrant numberCountry
Not funded
CitationJournal: To Be Published
Title: Structure of Cul2-VCB-Protac-Wee1 complex at 3.6 Angstrom resolution.
Authors: Wang, P. / Zhang, T.T.
History
DepositionSep 15, 2023Deposition site: PDBJ / Processing site: PDBJ
Revision 1.0Sep 18, 2024Provider: repository / Type: Initial release
Revision 1.1Oct 16, 2024Group: Data collection / Structure summary
Category: em_admin / pdbx_entry_details / pdbx_modification_feature
Item: _em_admin.last_update / _pdbx_entry_details.has_protein_modification

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Cullin-2
R: E3 ubiquitin-protein ligase RBX1, N-terminally processed
V: von Hippel-Lindau disease tumor suppressor
B: Elongin-B
C: Elongin-C
W: Wee1-like protein kinase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)170,6067
Polymers169,5636
Non-polymers1,0431
Water00
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: electron microscopy, not applicable
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1

-
Components

-
Protein , 6 types, 6 molecules ARVBCW

#1: Protein Cullin-2


Mass: 87098.930 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: CUL2
Production host: Insect cell expression vector pTIE1 (others)
References: UniProt: Q13617
#2: Protein E3 ubiquitin-protein ligase RBX1, N-terminally processed / E3 ubiquitin-protein transferase RBX1 / N-terminally processed


Mass: 9634.012 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: RBX1
Production host: Insect cell expression vector pTIE1 (others)
References: UniProt: P62877
#3: Protein von Hippel-Lindau disease tumor suppressor


Mass: 18012.527 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: VHL / Production host: Escherichia coli (E. coli) / References: UniProt: P40337
#4: Protein Elongin-B / EloB / Elongin 18 kDa subunit / RNA polymerase II transcription factor SIII subunit B / SIII p18 / ...EloB / Elongin 18 kDa subunit / RNA polymerase II transcription factor SIII subunit B / SIII p18 / Transcription elongation factor B polypeptide 2


Mass: 11748.406 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: ELOB, TCEB2 / Production host: Escherichia coli (E. coli) / References: UniProt: Q15370
#5: Protein Elongin-C


Mass: 10843.420 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: ELOC / Production host: Escherichia coli (E. coli) / References: UniProt: Q15369
#6: Protein Wee1-like protein kinase


Mass: 32225.691 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: WEE1 / Production host: Escherichia coli (E. coli) / References: UniProt: P30291

-
Non-polymers , 1 types, 1 molecules

#7: Chemical ChemComp-W6U / (2S,4R)-1-[(2S)-3,3-dimethyl-2-[3-[4-[4-[4-[[3-oxidanylidene-1-[6-(2-oxidanylpropan-2-yl)pyridin-2-yl]-2-prop-2-enyl-pyrazolo[3,4-d]pyrimidin-6-yl]amino]phenyl]piperazin-1-yl]butoxy]propanoylamino]butanoyl]-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]-4-oxidanyl-pyrrolidine-2-carboxamide


Mass: 1043.285 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C55H70N12O7S / Feature type: SUBJECT OF INVESTIGATION

-
Details

Has ligand of interestY
Has protein modificationY

-
Experimental details

-
Experiment

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

-
Sample preparation

ComponentName: Holo E3 complex including Cullin2, RBX1, VHL, ElongingB and ElonginC bound with Wee1 mediated by protac
Type: COMPLEX / Entity ID: #1-#6 / Source: RECOMBINANT
Source (natural)Organism: Homo sapiens (human)
Source (recombinant)Organism: Escherichia coli (E. coli)
Buffer solutionpH: 8
SpecimenEmbedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
VitrificationCryogen name: ETHANE

-
Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyModel: FEI TITAN KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELD / Nominal defocus max: 310 nm / Nominal defocus min: 150 nm
Image recordingElectron dose: 1.275 e/Å2 / Film or detector model: GATAN K3 (6k x 4k)

-
Processing

CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
3D reconstructionResolution: 3.64 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 312419 / Symmetry type: POINT

+
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