[English] 日本語
Yorodumi
- PDB-7q2j: Quaternary Complex of human WDR5 and pVHL:ElonginC:ElonginB bound... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7q2j
TitleQuaternary Complex of human WDR5 and pVHL:ElonginC:ElonginB bound to PROTAC Homer
Components
  • Elongin-B
  • Elongin-C
  • WD repeat-containing protein 5
  • von Hippel-Lindau disease tumor suppressor
KeywordsSTRUCTURAL PROTEIN / PROTAC / WDR5 / VHL / Quaternary Complex / Structural Genomics / Structural Genomics Consortium / SGC
Function / homology
Function and homology information


regulation of cellular response to hypoxia / histone H3Q5ser reader activity / histone H3K4me1 reader activity / RHOBTB3 ATPase cycle / negative regulation of receptor signaling pathway via JAK-STAT / Epigenetic regulation of gene expression by MLL3 and MLL4 complexes / MLL3/4 complex / transcription elongation factor activity / target-directed miRNA degradation / Set1C/COMPASS complex ...regulation of cellular response to hypoxia / histone H3Q5ser reader activity / histone H3K4me1 reader activity / RHOBTB3 ATPase cycle / negative regulation of receptor signaling pathway via JAK-STAT / Epigenetic regulation of gene expression by MLL3 and MLL4 complexes / MLL3/4 complex / transcription elongation factor activity / target-directed miRNA degradation / Set1C/COMPASS complex / MLL1/2 complex / elongin complex / ATAC complex / NSL complex / histone H3K4 methyltransferase activity / Replication of the SARS-CoV-1 genome / Cardiogenesis / VCB complex / Cul5-RING ubiquitin ligase complex / Cul2-RING ubiquitin ligase complex / intracellular membraneless organelle / Formation of WDR5-containing histone-modifying complexes / SUMOylation of ubiquitinylation proteins / histone methyltransferase complex / regulation of cell division / MLL1 complex / Pausing and recovery of Tat-mediated HIV elongation / Tat-mediated HIV elongation arrest and recovery / negative regulation of transcription elongation by RNA polymerase II / regulation of embryonic development / histone acetyltransferase complex / HIV elongation arrest and recovery / Pausing and recovery of HIV elongation / negative regulation of signal transduction / Tat-mediated elongation of the HIV-1 transcript / Formation of HIV-1 elongation complex containing HIV-1 Tat / ubiquitin-like ligase-substrate adaptor activity / Formation of HIV elongation complex in the absence of HIV Tat / RNA Polymerase II Transcription Elongation / Formation of RNA Pol II elongation complex / negative regulation of TORC1 signaling / RNA Polymerase II Pre-transcription Events / positive regulation of gluconeogenesis / transcription initiation-coupled chromatin remodeling / protein serine/threonine kinase binding / negative regulation of autophagy / transcription corepressor binding / gluconeogenesis / skeletal system development / positive regulation of cell differentiation / TP53 Regulates Transcription of DNA Repair Genes / transcription initiation at RNA polymerase II promoter / transcription elongation by RNA polymerase II / Vif-mediated degradation of APOBEC3G / RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function / Inactivation of CSF3 (G-CSF) signaling / Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha / Evasion by RSV of host interferon responses / PKMTs methylate histone lysines / Regulation of expression of SLITs and ROBOs / RMTs methylate histone arginines / Activation of anterior HOX genes in hindbrain development during early embryogenesis / cell morphogenesis / ubiquitin-protein transferase activity / mitotic spindle / transcription corepressor activity / Antigen processing: Ubiquitination & Proteasome degradation / positive regulation of proteasomal ubiquitin-dependent protein catabolic process / HATs acetylate histones / Neddylation / microtubule cytoskeleton / MLL4 and MLL3 complexes regulate expression of PPARG target genes in adipogenesis and hepatic steatosis / regulation of gene expression / protein-containing complex assembly / Replication of the SARS-CoV-2 genome / ubiquitin-dependent protein catabolic process / histone binding / protein-macromolecule adaptor activity / cellular response to hypoxia / DNA-binding transcription factor binding / molecular adaptor activity / amyloid fibril formation / proteasome-mediated ubiquitin-dependent protein catabolic process / regulation of cell cycle / protein stabilization / protein ubiquitination / cilium / negative regulation of cell population proliferation / negative regulation of gene expression / ubiquitin protein ligase binding / regulation of DNA-templated transcription / regulation of transcription by RNA polymerase II / negative regulation of apoptotic process / positive regulation of DNA-templated transcription / enzyme binding / endoplasmic reticulum / negative regulation of transcription by RNA polymerase II / mitochondrion / proteolysis / nucleoplasm
Similarity search - Function
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 / WDR5 beta-propeller domain / Elongin-C ...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 / WDR5 beta-propeller domain / Elongin-C / Elongin B / S-phase kinase-associated protein 1-like / SKP1 component, POZ domain / Skp1 family, tetramerisation domain / Found in Skp1 protein family / Phosphatidylinositol 3-kinase Catalytic Subunit; Chain A, domain 1 / SKP1/BTB/POZ domain superfamily / Ubiquitin-like (UB roll) / Ubiquitin family / Ubiquitin homologues / Ubiquitin domain profile. / Ubiquitin-like domain / Ubiquitin-like domain superfamily / G-protein beta WD-40 repeat / WD40 repeat, conserved site / Trp-Asp (WD) repeats signature. / Trp-Asp (WD) repeats profile. / Trp-Asp (WD) repeats circular profile. / WD40 repeats / WD40 repeat / WD40-repeat-containing domain superfamily / WD40/YVTN repeat-like-containing domain superfamily / Roll / Alpha Beta
Similarity search - Domain/homology
Chem-8KH / von Hippel-Lindau disease tumor suppressor / WD repeat-containing protein 5 / Elongin-C / Elongin-B
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / molecular replacement / Resolution: 2.5 Å
AuthorsKraemer, A. / Doelle, A. / Schwalm, M.P. / Adhikari, B. / Wolf, E. / Knapp, S. / Structural Genomics Consortium (SGC)
Funding support Germany, 1items
OrganizationGrant numberCountry
German Research Foundation (DFG) Germany
CitationJournal: Cell Chem Biol / Year: 2023
Title: Tracking the PROTAC degradation pathway in living cells highlights the importance of ternary complex measurement for PROTAC optimization.
Authors: Schwalm, M.P. / Kramer, A. / Dolle, A. / Weckesser, J. / Yu, X. / Jin, J. / Saxena, K. / Knapp, S.
History
DepositionOct 25, 2021Deposition site: PDBE / Processing site: PDBE
Revision 1.0Nov 24, 2021Provider: repository / Type: Initial release
Revision 1.1Nov 22, 2023Group: Data collection / Database references / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / citation / citation_author / refine
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year / _refine.pdbx_diffrn_id
Revision 1.2Jan 31, 2024Group: Refinement description / Category: pdbx_initial_refinement_model

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Elongin-B
B: Elongin-C
C: von Hippel-Lindau disease tumor suppressor
D: WD repeat-containing protein 5
hetero molecules


Theoretical massNumber of molelcules
Total (without water)80,5295
Polymers79,5164
Non-polymers1,0121
Water43224
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area5730 Å2
ΔGint-38 kcal/mol
Surface area27190 Å2
Unit cell
Length a, b, c (Å)47.702, 190.809, 48.698
Angle α, β, γ (deg.)90.000, 115.250, 90.000
Int Tables number4
Space group name H-MP1211

-
Components

-
Protein , 4 types, 4 molecules ABCD

#1: 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 BL21(DE3) (bacteria) / References: UniProt: Q15370
#2: Protein Elongin-C / EloC / Elongin 15 kDa subunit / RNA polymerase II transcription factor SIII subunit C / SIII p15 / ...EloC / Elongin 15 kDa subunit / RNA polymerase II transcription factor SIII subunit C / SIII p15 / Transcription elongation factor B polypeptide 1


Mass: 10974.616 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: ELOC, TCEB1 / Production host: Escherichia coli BL21(DE3) (bacteria) / References: UniProt: Q15369
#3: Protein von Hippel-Lindau disease tumor suppressor / Protein G7 / pVHL


Mass: 22503.463 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 BL21(DE3) (bacteria) / References: UniProt: P40337
#4: Protein WD repeat-containing protein 5 / BMP2-induced 3-kb gene protein


Mass: 34289.887 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Details: ...Details: GTQSKPTPVKPNYALKFTLAGHTKAVSSVKFSPNGEWLASSSADKLIKIWGAYDGKFEKTISGHKLGISDVAWSSDSNLLVSASDDKTLKIWDVSSGKCLKTLKGHSNYVFCCNFNPQSNLIVSGSFDESVRIWDVKTGKCLKTLPAHSDPVSAVHFNRDGSLIVSSSYDGLCRIWDTASGQCLKTLIDDDNPPVSFVKFSPNGKYILAATLDNTLKLWDYSKGKCLKTYTGHKNEKYCIFANFSVTGGKWIVSGSEDNLVYIWNLQTKEIVQKLQGHTDVVISTACHPTENIIASAALENDKTIKLWKSDC
Source: (gene. exp.) Homo sapiens (human) / Gene: WDR5, BIG3 / Production host: Escherichia coli BL21(DE3) (bacteria) / References: UniProt: P61964

-
Non-polymers , 2 types, 25 molecules

#5: Chemical ChemComp-8KH / N-[5-[4-[[5-[[(2S)-3,3-dimethyl-1-[(2S,4R)-2-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methylcarbamoyl]-4-oxidanyl-pyrrolidin-1-yl]-1-oxidanylidene-butan-2-yl]amino]-5-oxidanylidene-pentyl]carbamoyl]phenyl]-2-(4-methylpiperazin-1-yl)phenyl]-6-oxidanylidene-4-(trifluoromethyl)-1H-pyridine-3-carboxamide / Homer (chemical degrader probe)


Mass: 1012.149 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C52H60F3N9O7S / Feature type: SUBJECT OF INVESTIGATION
#6: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 24 / Source method: isolated from a natural source / Formula: H2O

-
Details

Has ligand of interestY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.52 Å3/Da / Density % sol: 51.21 %
Crystal growTemperature: 293 K / Method: vapor diffusion, sitting drop / pH: 6.8 / Details: 21% PEG 3350 0.4 M KSCN 0.1 M HEPES 6.8

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: SLS / Beamline: X06SA / Wavelength: 0.999998 Å
DetectorType: DECTRIS EIGER X 16M / Detector: PIXEL / Date: Dec 18, 2020
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.999998 Å / Relative weight: 1
ReflectionResolution: 2.5→47.75 Å / Num. obs: 26976 / % possible obs: 99.3 % / Redundancy: 7.1 % / CC1/2: 0.997 / Net I/σ(I): 8.8
Reflection shellResolution: 2.5→2.6 Å / Num. unique obs: 3045 / CC1/2: 0.786

-
Phasing

PhasingMethod: molecular replacement

-
Processing

Software
NameVersionClassificationNB
XDSdata reduction
Aimlessdata scaling
PHASERphasing
REFMAC5.8.0267refinement
PDB_EXTRACT3.27data extraction
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 2H9M

2h9m


Resolution: 2.5→47.75 Å / Cor.coef. Fo:Fc: 0.944 / Cor.coef. Fo:Fc free: 0.921 / SU B: 28.091 / SU ML: 0.481 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.596 / ESU R Free: 0.332 / Stereochemistry target values: MAXIMUM LIKELIHOOD
Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : REFINED INDIVIDUALLY
RfactorNum. reflection% reflectionSelection details
Rfree0.2932 1368 5.1 %RANDOM
Rwork0.2434 ---
obs0.2459 25571 99.3 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK
Displacement parametersBiso max: 134.86 Å2 / Biso mean: 67.574 Å2 / Biso min: 28.08 Å2
Baniso -1Baniso -2Baniso -3
1--6.83 Å20 Å20.99 Å2
2---9.07 Å20 Å2
3---10.36 Å2
Refinement stepCycle: final / Resolution: 2.5→47.75 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms4932 0 72 24 5028
Biso mean--65.98 47.23 -
Num. residues----642
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0050.0135129
X-RAY DIFFRACTIONr_bond_other_d0.0030.0154699
X-RAY DIFFRACTIONr_angle_refined_deg1.4291.6376999
X-RAY DIFFRACTIONr_angle_other_deg1.1831.59410822
X-RAY DIFFRACTIONr_dihedral_angle_1_deg7.5225637
X-RAY DIFFRACTIONr_dihedral_angle_2_deg34.54322.692234
X-RAY DIFFRACTIONr_dihedral_angle_3_deg19.62915791
X-RAY DIFFRACTIONr_dihedral_angle_4_deg23.4421524
X-RAY DIFFRACTIONr_chiral_restr0.0540.2688
X-RAY DIFFRACTIONr_gen_planes_refined0.0050.025959
X-RAY DIFFRACTIONr_gen_planes_other0.0020.021145
LS refinement shellResolution: 2.5→2.565 Å / Rfactor Rfree error: 0 / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.474 104 -
Rwork0.467 1896 -
all-2000 -
obs--99.6 %

+
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