[English] 日本語
Yorodumi
- EMDB-54794: Structure of RBR E2 variant binding to CUL5-RBX2 bound ARIH2 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-54794
TitleStructure of RBR E2 variant binding to CUL5-RBX2 bound ARIH2
Map data
Sample
  • Complex: NEDD8-CUL5-RBX2-ARIH2-E2V
    • Protein or peptide: L3A2-1
    • Protein or peptide: RING-box protein 2
    • Protein or peptide: Cullin-5
    • Protein or peptide: E3 ubiquitin-protein ligase ARIH2
  • Ligand: ZINC ION
KeywordsComplex / Ligase
Function / homology
Function and homology information


developmental cell growth / RBR-type E3 ubiquitin transferase / ERBB2 signaling pathway / reelin-mediated signaling pathway / cullin-RING-type E3 NEDD8 transferase / NEDD8 transferase activity / regulation of neuron migration / protein K11-linked ubiquitination / protein neddylation / ubiquitin conjugating enzyme binding ...developmental cell growth / RBR-type E3 ubiquitin transferase / ERBB2 signaling pathway / reelin-mediated signaling pathway / cullin-RING-type E3 NEDD8 transferase / NEDD8 transferase activity / regulation of neuron migration / protein K11-linked ubiquitination / protein neddylation / ubiquitin conjugating enzyme binding / NEDD8 ligase activity / response to redox state / : / Cul5-RING ubiquitin ligase complex / SCF ubiquitin ligase complex / SCF-dependent proteasomal ubiquitin-dependent protein catabolic process / hematopoietic stem cell proliferation / ubiquitin ligase complex scaffold activity / cullin family protein binding / site of DNA damage / protein K63-linked ubiquitination / ubiquitin ligase complex / protein K48-linked ubiquitination / endoplasmic reticulum unfolded protein response / intrinsic apoptotic signaling pathway / post-translational protein modification / G1/S transition of mitotic cell cycle / Vif-mediated degradation of APOBEC3G / RING-type E3 ubiquitin transferase / Inactivation of CSF3 (G-CSF) signaling / Evasion by RSV of host interferon responses / calcium channel activity / Downregulation of ERBB2 signaling / protein polyubiquitination / ubiquitin-protein transferase activity / ubiquitin protein ligase activity / Antigen processing: Ubiquitination & Proteasome degradation / signaling receptor activity / Neddylation / ubiquitin-dependent protein catabolic process / protein-macromolecule adaptor activity / proteasome-mediated ubiquitin-dependent protein catabolic process / protein ubiquitination / copper ion binding / ubiquitin protein ligase binding / zinc ion binding / nucleoplasm / nucleus / cytosol / cytoplasm
Similarity search - Function
: / : / Ariadne domain / Ariadne domain / E3 ubiquitin ligase RBR family / IBR domain, a half RING-finger domain / IBR domain / IBR domain / In Between Ring fingers / TRIAD supradomain ...: / : / Ariadne domain / Ariadne domain / E3 ubiquitin ligase RBR family / IBR domain, a half RING-finger domain / IBR domain / IBR domain / In Between Ring fingers / TRIAD supradomain / TRIAD supradomain profile. / 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 / Cullin / Cullin, N-terminal / Cullin homology domain / Cullin homology domain superfamily / Cullin alpha solenoid domain / Cullin family profile. / Zinc finger, C3HC4 RING-type / Zinc finger, C3HC4 type (RING finger) / Zinc finger, RING-type, conserved site / Zinc finger RING-type signature. / Ring finger / 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 ARIH2 / Cullin-5 / RING-box protein 2
Similarity search - Component
Biological speciesHomo sapiens (human) / synthetic construct (others)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.06 Å
AuthorsSchulman BA / Du J
Funding support Germany, 1 items
OrganizationGrant numberCountry
German Research Foundation (DFG)SCHU3196/1-1 Germany
CitationJournal: Proc Natl Acad Sci U S A / Year: 2026
Title: E2 variants for probing E3 ubiquitin ligase activities.
Authors: Jiale Du / Gisele A Andree / Daniel Horn-Ghetko / Luca Stier / Jaspal Singh / Sebastian Kostrhon / Leo Kiss / Matthias Mann / Sachdev S Sidhu / Brenda A Schulman /
Abstract: E3 ligases partner with E2 enzymes to regulate vast eukaryotic biology. The hierarchical nature of these pairings, with >600 E3s and ~40 E2s in humans, necessitates that E2s cofunction with numerous ...E3 ligases partner with E2 enzymes to regulate vast eukaryotic biology. The hierarchical nature of these pairings, with >600 E3s and ~40 E2s in humans, necessitates that E2s cofunction with numerous different E3s. Here, focusing on E3s in the RING-between-RING (RBR) family and their partner UBE2L3 and UBE2D-family E2s, we report an approach to interrogate selected pathways. We screened phage-displayed libraries of structure-based E2 variants (E2Vs) to discover enzymes with enhanced affinity and specificity toward half of all RBR E3 ligases (ARIH1, ARIH2, ANKIB1, CUL9, HOIL1, HOIP, and RNF14). Collectively, these E2Vs allowed distinguishing actions of different cofunctioning E3s, obtaining high-resolution cryogenic Electron Microscopy (cryo-EM) structures of an RBR E3 in the context of a substrate-bound multiprotein complex, and profiling an endogenous RBR E3 response to an extracellular stimulus. Overall, we anticipate that E2V technology will be a generalizable tool to enable in-depth mechanistic and structural analysis of E3 ligase functions, and mapping their activity states and protein partners in cellular signaling cascades.
History
DepositionAug 15, 2025-
Header (metadata) releaseDec 24, 2025-
Map releaseDec 24, 2025-
UpdateJan 14, 2026-
Current statusJan 14, 2026Processing site: PDBe / Status: Released

-
Structure visualization

Supplemental images

emd_54794.png

Downloads & links

-
Map

FileDownload / File: emd_54794.map.gz / Format: CCP4 / Size: 307.5 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.85 Å/pix.
x 432 pix.
= 367.718 Å		0.85 Å/pix.
x 432 pix.
= 367.718 Å		0.85 Å/pix.
x 432 pix.
= 367.718 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.8512 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.14
Minimum - Maximum-0.037036724 - 0.74711055
Average (Standard dev.)0.0021889557 (±0.012030967)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions432432432
Spacing432432432
CellA=B=C: 367.71838 Å
α=β=γ: 90.0 °

-
Supplemental data

-
Mask #1

Fileemd_54794_msk_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Additional map: #3

Fileemd_54794_additional_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Additional map: #2

Fileemd_54794_additional_2.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Additional map: #1

Fileemd_54794_additional_3.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: #2

Fileemd_54794_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: #1

Fileemd_54794_half_map_2.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Sample components

-
Entire : NEDD8-CUL5-RBX2-ARIH2-E2V

EntireName: NEDD8-CUL5-RBX2-ARIH2-E2V
Components
  • Complex: NEDD8-CUL5-RBX2-ARIH2-E2V
    • Protein or peptide: L3A2-1
    • Protein or peptide: RING-box protein 2
    • Protein or peptide: Cullin-5
    • Protein or peptide: E3 ubiquitin-protein ligase ARIH2
  • Ligand: ZINC ION

-
Supramolecule #1: NEDD8-CUL5-RBX2-ARIH2-E2V

SupramoleculeName: NEDD8-CUL5-RBX2-ARIH2-E2V / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#4
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 200 kDa/nm

-
Macromolecule #1: L3A2-1

MacromoleculeName: L3A2-1 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: synthetic construct (others)
Molecular weightTheoretical: 17.854475 KDa
Recombinant expressionOrganism: Escherichia coli (E. coli)
SequenceString:
MVAASSRLMK ELEEIRKAGM KNFRNIQVDE ANLLTWQGLI VPDNPPYDKG AFRIEINFPA EYPFKPPKIT FKTKIYHPNI DEKGQVCLP VISAENWKPA TKTDQVIQSL IALVNDPQPE HPLRADLAEE YSKDRKKFAK NAEEFTKKYG EKRPVD

-
Macromolecule #2: RING-box protein 2

MacromoleculeName: RING-box protein 2 / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO / EC number: RING-type E3 ubiquitin transferase
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 12.697436 KDa
Recombinant expressionOrganism: Trichoplusia ni (cabbage looper)
SequenceString:
MADVEDGEET CALASHSGSS GSKSGGDKMF SLKKWNAVAM WSWDVECDTC AICRVQVMDA CLRCQAENKQ EDCVVVWGEC NHSFHNCCM SLWVKQNNRC PLCQQDWVVQ RIGK

UniProtKB: RING-box protein 2

-
Macromolecule #3: Cullin-5

MacromoleculeName: Cullin-5 / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 91.085297 KDa
Recombinant expressionOrganism: Trichoplusia ni (cabbage looper)
SequenceString: MATSNLLKNK GSLQFEDKWD FMRPIVLKLL RQESVTKQQW FDLFSDVHAV CLWDDKGPAK IHQALKEDIL EFIKQAQARV LSHQDDTAL LKAYIVEWRK FFTQCDILPK PFCQLEITLM GKQGSNKKSN VEDSIVRKLM LDTWNESIFS NIKNRLQDSA M KLVHAERL ...String:
MATSNLLKNK GSLQFEDKWD FMRPIVLKLL RQESVTKQQW FDLFSDVHAV CLWDDKGPAK IHQALKEDIL EFIKQAQARV LSHQDDTAL LKAYIVEWRK FFTQCDILPK PFCQLEITLM GKQGSNKKSN VEDSIVRKLM LDTWNESIFS NIKNRLQDSA M KLVHAERL GEAFDSQLVI GVRESYVNLC SNPEDKLQIY RDNFEKAYLD STERFYRTQA PSYLQQNGVQ NYMKYADAKL KE EEKRALR YLETRRECNS VEALMECCVN ALVTSFKETI LAECQGMIKR NETEKLHLMF SLMDKVPNGI EPMLKDLEEH IIS AGLADM VAAAETITTD SEKYVEQLLT LFNRFSKLVK EAFQDDPRFL TARDKAYKAV VNDATIFKLE LPLKQKGVGL KTQP ESKCP ELLANYCDML LRKTPLSKKL TSEEIEAKLK EVLLVLKYVQ NKDVFMRYHK AHLTRRLILD ISADSEIEEN MVEWL REVG MPADYVNKLA RMFQDIKVSE DLNQAFKEMH KNNKLALPAD SVNIKILNAG AWSRSSEKVF VSLPTELEDL IPEVEE FYK KNHSGRKLHW HHLMSNGIIT FKNEVGQYDL EVTTFQLAVL FAWNQRPREK ISFENLKLAT ELPDAELRRT LWSLVAF PK LKRQVLLYEP QVNSPKDFTE GTLFSVNQEF SLIKNAKVQK RGKINLIGRL QLTTERMREE ENEGIVQLRI LRTQEAII Q IMKMRKKISN AQLQTELVEI LKNMFLPQKK MIKEQIEWLI EHKYIRRDES DINTFIYMA

UniProtKB: Cullin-5

-
Macromolecule #4: E3 ubiquitin-protein ligase ARIH2

MacromoleculeName: E3 ubiquitin-protein ligase ARIH2 / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO / EC number: RBR-type E3 ubiquitin transferase
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 57.893844 KDa
Recombinant expressionOrganism: Escherichia coli (E. coli)
SequenceString: MSVDMNSQGS DSNEEDYDPN CEEEEEEEED DPGDIEDYYV GVASDVEQQG ADAFDPEEYQ FTCLTYKESE GALNEHMTSL ASVLKVSHS VAKLILVNFH WQVSEILDRY KSNSAQLLVE ARVQPNPSKH VPTSHPPHHC AVCMQFVRKE NLLSLACQHQ F CRSCWEQH ...String:
MSVDMNSQGS DSNEEDYDPN CEEEEEEEED DPGDIEDYYV GVASDVEQQG ADAFDPEEYQ FTCLTYKESE GALNEHMTSL ASVLKVSHS VAKLILVNFH WQVSEILDRY KSNSAQLLVE ARVQPNPSKH VPTSHPPHHC AVCMQFVRKE NLLSLACQHQ F CRSCWEQH CSVLVKDGVG VGVSCMAQDC PLRTPEDFVF PLLPNEELRE KYRRYLFRDY VESHYQLQLC PGADCPMVIR VQ EPRARRV QCNRCNEVFC FKCRQMYHAP TDCATIRKWL TKCADDSETA NYISAHTKDC PKCNICIEKN GGCNHMQCSK CKH DFCWMC LGDWKTHGSE YYECSRYKEN PDIVNQSQQA QAREALKKYL FYFERWENHN KSLQLEAQTY QRIHEKIQER VMNN LGTWI DWQYLQNAAK LLAKCRYTLQ YTYPYAYYME SGPRKKLFEY QQAQLEAEIE NLSWKVERAD SYDRGDLENQ MHIAE QRRR TLLKDFHDT

UniProtKB: E3 ubiquitin-protein ligase ARIH2

-
Macromolecule #5: ZINC ION

MacromoleculeName: ZINC ION / type: ligand / ID: 5 / Number of copies: 7 / Formula: ZN
Molecular weightTheoretical: 65.409 Da

-
Experimental details

-
Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

-
Sample preparation

BufferpH: 7.5
VitrificationCryogen name: ETHANE-PROPANE

-
Electron microscopy

MicroscopeTFS KRIOS
Image recordingFilm or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 60.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.6 µm / Nominal defocus min: 1.0 µm
Sample stageCooling holder cryogen: NITROGEN
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

+
Image processing

CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Startup modelType of model: PDB ENTRY
PDB model - PDB ID:

8oni

Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.06 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC / Number images used: 191502
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD
FSC plot (resolution estimation)

+
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