[English] 日本語
Yorodumi
- PDB-9n88: PROTAC-induced IRE1 ternary complex -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 9n88
TitlePROTAC-induced IRE1 ternary complex
Components
  • Elongin-B peptide
  • Elongin-C
  • Serine/threonine-protein kinase/endoribonuclease IRE1
  • von Hippel-Lindau disease tumor suppressor
KeywordsTRANSFERASE / Complex / degrader
Function / homology
Function and homology information


peptidyl-serine trans-autophosphorylation / mRNA splicing, via endonucleolytic cleavage and ligation / AIP1-IRE1 complex / Ire1 complex / IRE1alpha activates chaperones / IRE1-TRAF2-ASK1 complex / insulin metabolic process / regulation of cellular response to hypoxia / positive regulation of endoplasmic reticulum unfolded protein response / RHOBTB3 ATPase cycle ...peptidyl-serine trans-autophosphorylation / mRNA splicing, via endonucleolytic cleavage and ligation / AIP1-IRE1 complex / Ire1 complex / IRE1alpha activates chaperones / IRE1-TRAF2-ASK1 complex / insulin metabolic process / regulation of cellular response to hypoxia / positive regulation of endoplasmic reticulum unfolded protein response / RHOBTB3 ATPase cycle / negative regulation of receptor signaling pathway via JAK-STAT / transcription elongation factor activity / target-directed miRNA degradation / elongin complex / IRE1-RACK1-PP2A complex / platelet-derived growth factor receptor binding / nuclear inner membrane / endothelial cell proliferation / Hydrolases; Acting on ester bonds; Endoribonucleases producing 5'-phosphomonoesters / Replication of the SARS-CoV-1 genome / VCB complex / Cul5-RING ubiquitin ligase complex / Cul2-RING ubiquitin ligase complex / intracellular membraneless organelle / IRE1-mediated unfolded protein response / SUMOylation of ubiquitinylation proteins / mRNA catabolic process / positive regulation of JUN kinase activity / Pausing and recovery of Tat-mediated HIV elongation / Tat-mediated HIV elongation arrest and recovery / negative regulation of transcription elongation by RNA polymerase II / HIV elongation arrest and recovery / Pausing and recovery of HIV elongation / intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress / cellular response to vascular endothelial growth factor stimulus / cellular response to unfolded protein / regulation of macroautophagy / 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 / positive regulation of vascular associated smooth muscle cell proliferation / Formation of RNA Pol II elongation complex / negative regulation of TORC1 signaling / Hsp70 protein binding / RNA Polymerase II Pre-transcription Events / RNA endonuclease activity / negative regulation of autophagy / protein serine/threonine kinase binding / response to endoplasmic reticulum stress / positive regulation of RNA splicing / transcription corepressor binding / TP53 Regulates Transcription of DNA Repair Genes / transcription initiation at RNA polymerase II promoter / positive regulation of cell differentiation / transcription elongation by RNA polymerase II / cellular response to glucose stimulus / Hsp90 protein binding / Vif-mediated degradation of APOBEC3G / Inactivation of CSF3 (G-CSF) signaling / ADP binding / Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha / Evasion by RSV of host interferon responses / Regulation of expression of SLITs and ROBOs / cellular response to hydrogen peroxide / cell morphogenesis / ubiquitin-protein transferase activity / transcription corepressor activity / unfolded protein binding / Antigen processing: Ubiquitination & Proteasome degradation / positive regulation of proteasomal ubiquitin-dependent protein catabolic process / Neddylation / microtubule cytoskeleton / regulation of gene expression / protein-containing complex assembly / Replication of the SARS-CoV-2 genome / ubiquitin-dependent protein catabolic process / protein-macromolecule adaptor activity / cellular response to hypoxia / molecular adaptor activity / DNA-binding transcription factor binding / amyloid fibril formation / proteasome-mediated ubiquitin-dependent protein catabolic process / protein phosphorylation / non-specific serine/threonine protein kinase / protein stabilization / protein ubiquitination / cilium / negative regulation of cell population proliferation / negative regulation of gene expression / protein serine kinase activity / protein serine/threonine kinase activity / ubiquitin protein ligase binding / regulation of DNA-templated transcription / regulation of transcription by RNA polymerase II / endoplasmic reticulum membrane / negative regulation of apoptotic process / positive regulation of DNA-templated transcription
Similarity search - Function
Serine/threonine-protein kinase/endoribonuclease IRE1/2-like / KEN domain / KEN domain superfamily / Ribonuclease 2-5A / KEN domain profile. / domain in protein kinases, N-glycanases and other nuclear proteins / 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 ...Serine/threonine-protein kinase/endoribonuclease IRE1/2-like / KEN domain / KEN domain superfamily / Ribonuclease 2-5A / KEN domain profile. / domain in protein kinases, N-glycanases and other nuclear proteins / 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 / Pyrrolo-quinoline quinone beta-propeller repeat / beta-propeller repeat / Elongin-C / Elongin B / S-phase kinase-associated protein 1-like / SKP1 component, POZ domain / Skp1 family, tetramerisation domain / Found in Skp1 protein family / Quinoprotein alcohol dehydrogenase-like superfamily / SKP1/BTB/POZ domain superfamily / Ubiquitin family / Ubiquitin homologues / Ubiquitin domain profile. / Ubiquitin-like domain / Ubiquitin-like domain superfamily / Serine/threonine-protein kinase, active site / Serine/Threonine protein kinases active-site signature. / Protein kinase domain / Serine/Threonine protein kinases, catalytic domain / WD40/YVTN repeat-like-containing domain superfamily / Protein kinase domain profile. / Protein kinase domain / Protein kinase-like domain superfamily
Similarity search - Domain/homology
: / Serine/threonine-protein kinase/endoribonuclease IRE1 / von Hippel-Lindau disease tumor suppressor / Elongin-C / Elongin-B
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.6 Å
AuthorsDu, J. / Johnson, M. / Azumaya, C. / Rohou, A. / Hsu, P.L. / Ashkenazi, A.
Funding support United States, 1items
OrganizationGrant numberCountry
Other private United States
CitationJournal: To Be Published
Title: PROTAC-induced IRE1 ternary complex
Authors: Du, J. / Johnson, M. / Azumaya, C. / Rohou, A. / Hsu, P.L. / Ashkenazi, A.
History
DepositionFeb 7, 2025Deposition site: RCSB / Processing site: RCSB
Revision 1.0Nov 5, 2025Provider: repository / Type: Initial release
Revision 1.0Nov 5, 2025Data content type: EM metadata / Data content type: EM metadata / Provider: repository / Type: Initial release
Revision 1.0Nov 5, 2025Data content type: FSC / Data content type: FSC / Provider: repository / Type: Initial release
Revision 1.0Nov 5, 2025Data content type: Half map / Part number: 1 / Data content type: Half map / Provider: repository / Type: Initial release
Revision 1.0Nov 5, 2025Data content type: Half map / Part number: 2 / Data content type: Half map / Provider: repository / Type: Initial release
Revision 1.0Nov 5, 2025Data content type: Image / Data content type: Image / Provider: repository / Type: Initial release
Revision 1.0Nov 5, 2025Data content type: Primary map / Data content type: Primary map / Provider: repository / Type: Initial release

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Serine/threonine-protein kinase/endoribonuclease IRE1
B: von Hippel-Lindau disease tumor suppressor
E: Serine/threonine-protein kinase/endoribonuclease IRE1
F: von Hippel-Lindau disease tumor suppressor
G: Elongin-C
C: Elongin-C
D: Elongin-B peptide
H: Elongin-B peptide
hetero molecules


Theoretical massNumber of molelcules
Total (without water)151,01710
Polymers149,2518
Non-polymers1,7662
Water1086
1


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

-
Components

-
Protein , 3 types, 6 molecules AEBFGC

#1: Protein Serine/threonine-protein kinase/endoribonuclease IRE1 / Endoplasmic reticulum-to-nucleus signaling 1 / Inositol-requiring protein 1 / hIRE1p / Ire1-alpha / IRE1a


Mass: 46329.266 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: ERN1, IRE1 / Cell line (production host): Sf9 / Production host: Spodoptera frugiperda (fall armyworm)
References: UniProt: O75460, non-specific serine/threonine protein kinase, Hydrolases; Acting on ester bonds; Endoribonucleases producing 5'-phosphomonoesters
#2: Protein von Hippel-Lindau disease tumor suppressor / Protein G7 / pVHL


Mass: 17031.412 Da / Num. of mol.: 2
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
#3: 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: 10625.190 Da / Num. of mol.: 2
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

-
Protein/peptide , 1 types, 2 molecules DH

#4: Protein/peptide Elongin-B peptide / 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: 639.723 Da / Num. of mol.: 2 / Fragment: 68-73
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

-
Non-polymers , 2 types, 8 molecules

#5: Chemical ChemComp-A1BWF / 3-methyl-N-(5-{4-[(1r,4S)-4-{[7-oxo-8-(propan-2-yl)-7,8-dihydropyrido[2,3-d]pyrimidin-2-yl]amino}cyclohexyl]piperazin-1-yl}pentanoyl)-L-valyl-(4R)-4-hydroxy-N-{[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl}-L-prolinamide


Mass: 883.156 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C47H66N10O5S / Feature type: SUBJECT OF INVESTIGATION
#6: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 6 / Source method: isolated from a natural source / Formula: H2O

-
Details

Has ligand of interestY
Has protein modificationN

-
Experimental details

-
Experiment

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

-
Sample preparation

ComponentName: IRE1:G6374:VHL:Eloc:Elob / Type: COMPLEX
Details: G6374 is the PROTAC that recruits VHL to IRE1. IRE1 is recombinantly expressed and purified from Sf9 cells, VHL is co-expressed and co-purified with Eloc and Elob in BL21 cells. The complex ...Details: G6374 is the PROTAC that recruits VHL to IRE1. IRE1 is recombinantly expressed and purified from Sf9 cells, VHL is co-expressed and co-purified with Eloc and Elob in BL21 cells. The complex was formed by adding each component in vitro. Because the EloB density had insufficient quality for de novo modeling, we built only residues 68 to 73 into the structure.
Entity ID: #1-#3 / Source: RECOMBINANT
Molecular weightExperimental value: NO
Source (natural)Organism: Homo sapiens (human)
Source (recombinant)Organism: Spodoptera frugiperda (fall armyworm) / Strain: Sf9
Buffer solutionpH: 7.2
Details: I used 0.5 mM BS3 for crosslinking the protein complex, then diluted it to 0.05 mM for grid preparation.
Buffer component
IDConc.NameFormulaBuffer-ID
120 mM4-(2-hydroxyethyl)-1-piperazineethanesulfonic acidHEPES1
2150 mMsodium chlorideNaCl1
31 mMtris(2-carboxyethyl)phosphineTCEP1
40.005 %cetrimonium bromideCTAB1
SpecimenConc.: 0.15 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES / Details: Got monodispersed particles on the grid.
Specimen supportDetails: The grid was coated with a hydrophilic self-assembled PEG monolayer to improve particle distribution.
Grid material: GOLD / Grid mesh size: 300 divisions/in. / Grid type: UltrAuFoil R1.2/1.3
VitrificationInstrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 277.15 K / Details: 7 force; 2 s blot time.

-
Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyModel: TFS KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELD / Nominal defocus max: 3500 nm / Nominal defocus min: 600 nm
Image recordingElectron dose: 45 e/Å2 / Film or detector model: TFS FALCON 4i (4k x 4k) / Num. of real images: 12400

-
Processing

EM software
IDNameVersionCategory
1cryoSPARC4.6particle selection
4cryoSPARC4.6CTF correction
9cryoSPARC4.6initial Euler assignment
10cryoSPARC4.6final Euler assignment
12cryoSPARC4.63D reconstruction
CTF correctionType: PHASE FLIPPING ONLY
Particle selectionNum. of particles selected: 5101645
SymmetryPoint symmetry: C2 (2 fold cyclic)
3D reconstructionResolution: 2.6 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 400055 / Symmetry type: POINT
RefinementHighest resolution: 2.6 Å
Stereochemistry target values: REAL-SPACE (WEIGHTED MAP SUM AT ATOM CENTERS)

+
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