[English] 日本語
Yorodumi
- EMDB-52616: Cryo-EM structure of the AGR2 dimer in complex with the monomeric... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-52616
TitleCryo-EM structure of the AGR2 dimer in complex with the monomeric IRE1beta luminal domain
Map data
Sample
  • Complex: The complex of AGR2 and IRE1beta luminal domain
    • Protein or peptide: Anterior gradient protein 2 homolog
    • Protein or peptide: Serine/threonine-protein kinase/endoribonuclease IRE2
Keywordsendoplasmic reticulum (ER) / molecular chaperones/ protein multimerisation/ unfolded protein response (UPR) / CHAPERONE
Function / homology
Function and homology information


lung goblet cell differentiation / positive regulation of PERK-mediated unfolded protein response / apoptotic chromosome condensation / IRE1-TRAF2-ASK1 complex / endoplasmic reticulum quality control compartment / mucus secretion / dystroglycan binding / rRNA catabolic process / positive regulation of developmental growth / Hydrolases; Acting on ester bonds; Endoribonucleases producing 5'-phosphomonoesters ...lung goblet cell differentiation / positive regulation of PERK-mediated unfolded protein response / apoptotic chromosome condensation / IRE1-TRAF2-ASK1 complex / endoplasmic reticulum quality control compartment / mucus secretion / dystroglycan binding / rRNA catabolic process / positive regulation of developmental growth / Hydrolases; Acting on ester bonds; Endoribonucleases producing 5'-phosphomonoesters / positive regulation of cell-substrate adhesion / epidermal growth factor receptor binding / positive regulation of epidermal growth factor receptor signaling pathway / IRE1-mediated unfolded protein response / digestive tract morphogenesis / positive regulation of IRE1-mediated unfolded protein response / intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress / RNA endonuclease activity / response to endoplasmic reticulum stress / positive regulation of protein localization to plasma membrane / mRNA processing / unfolded protein binding / endonuclease activity / protein phosphorylation / non-specific serine/threonine protein kinase / inflammatory response / protein serine kinase activity / negative regulation of DNA-templated transcription / protein serine/threonine kinase activity / positive regulation of gene expression / magnesium ion binding / endoplasmic reticulum / extracellular space / extracellular region / ATP binding / identical protein binding / cytosol
Similarity search - Function
: / Thioredoxin-like / 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 / Pyrrolo-quinoline quinone beta-propeller repeat / beta-propeller repeat ...: / Thioredoxin-like / 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 / Pyrrolo-quinoline quinone beta-propeller repeat / beta-propeller repeat / Quinoprotein alcohol dehydrogenase-like superfamily / Thioredoxin-like 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
Anterior gradient protein 2 homolog / Serine/threonine-protein kinase/endoribonuclease IRE2
Similarity search - Component
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 2.9 Å
AuthorsYan Y / Hardwick S / Tung J / Ron D
Funding support United Kingdom, 1 items
OrganizationGrant numberCountry
Wellcome TrustSGAG/182 United Kingdom
CitationJournal: Mol Cell / Year: 2025
Title: A structural basis for chaperone repression of stress signaling from the endoplasmic reticulum.
Authors: Lisa Neidhardt / Joanne Tung / Miriam Kuchersky / Jakub Milczarek / Vasileios Kargas / Katherine Stott / Rina Rosenzweig / David Ron / Yahui Yan /
Abstract: The endoplasmic reticulum (ER) unfolded protein response (UPR) is tuned by the balance between unfolded proteins and chaperones. Reserve chaperones suppress UPR transducers via their stress-sensing ...The endoplasmic reticulum (ER) unfolded protein response (UPR) is tuned by the balance between unfolded proteins and chaperones. Reserve chaperones suppress UPR transducers via their stress-sensing luminal domains, but the underlying mechanisms remain unclear. The ER chaperone AGR2 is known to repress the UPR transducer IRE1β. Here, structural prediction, X-ray crystallography, and NMR spectroscopy identify critical interactions between an AGR2 monomer and a regulatory loop in IRE1β's luminal domain. However, in the repressive complex, it is an AGR2 dimer that binds IRE1β. Cryoelectron microscopy (cryo-EM) reconstruction explains this feature: one AGR2 protomer engages the regulatory loop, while the second asymmetrically binds IRE1β's luminal domain's C terminus, blocking IRE1β-activating dimerization. Molecular dynamic simulations indicate that the second, disruptive AGR2 protomer exploits rare fluctuations in the IRE1β dimer that expose its binding site. Thus, AGR2 disrupts IRE1β dimers to suppress the UPR, priming the system for activation by chaperone clients that compete for AGR2.
History
DepositionJan 24, 2025-
Header (metadata) releaseOct 22, 2025-
Map releaseOct 22, 2025-
UpdateNov 19, 2025-
Current statusNov 19, 2025Processing site: PDBe / Status: Released

-
Structure visualization

Supplemental images

emd_52616.png

Downloads & links

-
Map

FileDownload / File: emd_52616.map.gz / Format: CCP4 / Size: 274.6 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.73 Å/pix.
x 416 pix.
= 303.264 Å		0.73 Å/pix.
x 416 pix.
= 303.264 Å		0.73 Å/pix.
x 416 pix.
= 303.264 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.729 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.1
Minimum - Maximum-0.11571237 - 0.38634348
Average (Standard dev.)0.00006561396 (±0.006317754)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions416416416
Spacing416416416
CellA=B=C: 303.26398 Å
α=β=γ: 90.0 °

-
Supplemental data

-
Half map: #2

Fileemd_52616_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: #1

Fileemd_52616_half_map_2.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Sample components

-
Entire : The complex of AGR2 and IRE1beta luminal domain

EntireName: The complex of AGR2 and IRE1beta luminal domain
Components
  • Complex: The complex of AGR2 and IRE1beta luminal domain
    • Protein or peptide: Anterior gradient protein 2 homolog
    • Protein or peptide: Serine/threonine-protein kinase/endoribonuclease IRE2

-
Supramolecule #1: The complex of AGR2 and IRE1beta luminal domain

SupramoleculeName: The complex of AGR2 and IRE1beta luminal domain / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all / Details: Co-expressed in E.coli.
Source (natural)Organism: Homo sapiens (human)

-
Macromolecule #1: Anterior gradient protein 2 homolog

MacromoleculeName: Anterior gradient protein 2 homolog / type: protein_or_peptide / ID: 1 / Number of copies: 2 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 17.845541 KDa
Recombinant expressionOrganism: Escherichia coli (E. coli)
SequenceString:
RDTTVKPGAK KDTKDSRPKL PQTLSRGWGD QLIWTQTYEE ALYKSKTSNK PLMIIHHLDE CPHSQALKKV FAENKEIQKL AEQFVLLNL VYETTDKHLS PDGQYVPRIM FVDPSLTVRA DITGRYSNRL YAYEPADTAL LLDNMKKALK LLKTEL

UniProtKB: Anterior gradient protein 2 homolog

-
Macromolecule #2: Serine/threonine-protein kinase/endoribonuclease IRE2

MacromoleculeName: Serine/threonine-protein kinase/endoribonuclease IRE2 / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO / EC number: non-specific serine/threonine protein kinase
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 43.393164 KDa
Recombinant expressionOrganism: Escherichia coli (E. coli)
SequenceString: LRPENLLLVS TLDGSLHALS KQTGDLKWTL RDDPVIEGPM YVTEMAFLSD PADGSLYILG TQKQQGLMKL PFTIPELVHA SPCRSSDGV FYTGRKQDAW FVVDPESGET QMTLTTEGPS TPRLYIGRTQ YTVTMHDPRA PALRWNTTYR RYSAPPMDGS P GKYMSHLA ...String:
LRPENLLLVS TLDGSLHALS KQTGDLKWTL RDDPVIEGPM YVTEMAFLSD PADGSLYILG TQKQQGLMKL PFTIPELVHA SPCRSSDGV FYTGRKQDAW FVVDPESGET QMTLTTEGPS TPRLYIGRTQ YTVTMHDPRA PALRWNTTYR RYSAPPMDGS P GKYMSHLA SCGMGLLLTV DPGSGTVLWT QDLGVPVMGV YTWHQDGLRQ LPHLTLARDT LHFLALRWGH IRLPASGPRD TA TLFSTLD TQLLMTLYVG KDETGFYVSK ALVHTGVALV PRGLTLAPAD GPTTDEVTLQ VSGEREGSPS TAVRYPSGSV ALP SQWLLI GHHELPPVLH TTMLRVHPTL GSGTAETRPP ENTQAPAFFL ELLSLSREKL WDSELHPEEK TPDSYLGLG

UniProtKB: Serine/threonine-protein kinase/endoribonuclease IRE2

-
Experimental details

-
Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

-
Sample preparation

Concentration3.2 mg/mL
BufferpH: 7.4
Component:
ConcentrationFormulaName
150.0 mMNaClsodium chloride
200.0 mMTristris(hydroxymethyl)aminomethane
0.2 mMTCEPtris(2-carboxyethyl)phosphine
GridModel: UltrAuFoil R0./1
VitrificationCryogen name: ETHANE / Chamber humidity: 95 % / Chamber temperature: 281.15 K / Instrument: FEI VITROBOT MARK IV
DetailsThe complex elutes as a peak cooresponding to a complex containing two copies of AGR2 and one copy of IRE1beta luminal domain.

-
Electron microscopy

MicroscopeTFS KRIOS
Image recordingFilm or detector model: FEI FALCON IV (4k x 4k) / Average electron dose: 11.95 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 1.8 µm / Nominal defocus min: 0.6 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

+
Image processing

CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Startup modelType of model: NONE
Final reconstructionResolution.type: BY AUTHOR / Resolution: 2.9 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC (ver. 4.6.0) / Number images used: 313426
Initial angle assignmentType: RANDOM ASSIGNMENT / Software - Name: cryoSPARC (ver. 4.6.0)
Final angle assignmentType: PROJECTION MATCHING / Software - Name: cryoSPARC (ver. 4.6.0)
Final 3D classificationSoftware - Name: cryoSPARC (ver. 4.6.0)
FSC plot (resolution estimation)

-
Atomic model buiding 1

Initial model
PDB IDChain

5-f1

residue_range: 35-429, source_name: AlphaFold, initial_model_type: in silico model

9i3f

chain_id: A, source_name: PDB, initial_model_type: experimental model

9i3f

chain_id: C, source_name: PDB, initial_model_type: experimental model
RefinementProtocol: RIGID BODY FIT
Output model

PDB-9i3u:
Cryo-EM structure of the AGR2 dimer in complex with the monomeric IRE1beta luminal domain

+
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