[English] 日本語
Yorodumi
- EMDB-12995: Structure of Neddylated CUL5 C-terminal region-RBX2-ARIH2* -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-12995
TitleStructure of Neddylated CUL5 C-terminal region-RBX2-ARIH2*
Map data
Sample
  • Complex: Neddylated CUL5 C-terminal region-RBX2-ARIH2
    • Protein or peptide: Cullin-5
    • Protein or peptide: E3 ubiquitin-protein ligase ARIH2
    • Protein or peptide: RING-box protein 2
    • Protein or peptide: NEDD8
  • Ligand: ZINC ION
KeywordsCUL5 / NEDD8 / UBQ / UBIQUITIN / ARIH2 / RBX2 / LIGASE
Function / homology
Function and homology information


developmental cell growth / RBR-type E3 ubiquitin transferase / ERBB2 signaling pathway / reelin-mediated signaling pathway / regulation of neuron migration / cullin-RING-type E3 NEDD8 transferase / NEDD8 transferase activity / regulation of proteolysis / protein K11-linked ubiquitination / protein neddylation ...developmental cell growth / RBR-type E3 ubiquitin transferase / ERBB2 signaling pathway / reelin-mediated signaling pathway / regulation of neuron migration / cullin-RING-type E3 NEDD8 transferase / NEDD8 transferase activity / regulation of proteolysis / protein K11-linked ubiquitination / protein neddylation / ubiquitin conjugating enzyme binding / NEDD8 ligase activity / Cul5-RING ubiquitin ligase complex / response to redox state / positive regulation of protein targeting to mitochondrion / SCF ubiquitin ligase complex / hematopoietic stem cell proliferation / SCF-dependent proteasomal ubiquitin-dependent protein catabolic process / ubiquitin ligase complex scaffold activity / TGF-beta receptor signaling activates SMADs / site of DNA damage / cullin family protein binding / protein K63-linked ubiquitination / anatomical structure morphogenesis / protein K48-linked ubiquitination / ubiquitin ligase complex / endoplasmic reticulum unfolded protein response / post-translational protein modification / intrinsic apoptotic signaling pathway / Iron uptake and transport / Vif-mediated degradation of APOBEC3G / protein modification process / RING-type E3 ubiquitin transferase / Inactivation of CSF3 (G-CSF) signaling / calcium channel activity / Evasion by RSV of host interferon responses / Downregulation of ERBB2 signaling / modification-dependent protein catabolic process / protein polyubiquitination / ubiquitin-protein transferase activity / G1/S transition of mitotic cell cycle / protein tag activity / UCH proteinases / ubiquitin protein ligase activity / protein localization / Antigen processing: Ubiquitination & Proteasome degradation / Cargo recognition for clathrin-mediated endocytosis / signaling receptor activity / Neddylation / protein-macromolecule adaptor activity / ubiquitin-dependent protein catabolic process / proteasome-mediated ubiquitin-dependent protein catabolic process / protein ubiquitination / copper ion binding / ubiquitin protein ligase binding / regulation of transcription by RNA polymerase II / proteolysis / extracellular exosome / zinc ion binding / nucleoplasm / nucleus / cytosol / cytoplasm
Similarity search - Function
: / : / Ariadne domain / Ariadne domain / IBR domain, a half RING-finger domain / Nedd8-like ubiquitin / E3 ubiquitin ligase RBR family / IBR domain / IBR domain / In Between Ring fingers ...: / : / Ariadne domain / Ariadne domain / IBR domain, a half RING-finger domain / Nedd8-like ubiquitin / E3 ubiquitin ligase RBR family / 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 family / 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 / : / Ubiquitin domain signature. / Ubiquitin conserved site / Ubiquitin domain / 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 / Winged helix-like DNA-binding domain superfamily
Similarity search - Domain/homology
E3 ubiquitin-protein ligase ARIH2 / NEDD8 / Cullin-5 / RING-box protein 2
Similarity search - Component
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.4 Å
AuthorsKostrhon SP / prabu JR
Funding support Germany, 3 items
OrganizationGrant numberCountry
Max Planck Society Germany
European Research Council (ERC)H2020 789016-NEDD8Activate Germany
German Research Foundation (DFG)SCHU 3196/1-1 Germany
CitationJournal: Nat Chem Biol / Year: 2021
Title: CUL5-ARIH2 E3-E3 ubiquitin ligase structure reveals cullin-specific NEDD8 activation.
Authors: Sebastian Kostrhon / J Rajan Prabu / Kheewoong Baek / Daniel Horn-Ghetko / Susanne von Gronau / Maren Klügel / Jérôme Basquin / Arno F Alpi / Brenda A Schulman /
Abstract: An emerging mechanism of ubiquitylation involves partnering of two distinct E3 ligases. In the best-characterized E3-E3 pathways, ARIH-family RING-between-RING (RBR) E3s ligate ubiquitin to ...An emerging mechanism of ubiquitylation involves partnering of two distinct E3 ligases. In the best-characterized E3-E3 pathways, ARIH-family RING-between-RING (RBR) E3s ligate ubiquitin to substrates of neddylated cullin-RING E3s. The E3 ARIH2 has been implicated in ubiquitylation of substrates of neddylated CUL5-RBX2-based E3s, including APOBEC3-family substrates of the host E3 hijacked by HIV-1 virion infectivity factor (Vif). However, the structural mechanisms remained elusive. Here structural and biochemical analyses reveal distinctive ARIH2 autoinhibition, and activation on assembly with neddylated CUL5-RBX2. Comparison to structures of E3-E3 assemblies comprising ARIH1 and neddylated CUL1-RBX1-based E3s shows cullin-specific regulation by NEDD8. Whereas CUL1-linked NEDD8 directly recruits ARIH1, CUL5-linked NEDD8 does not bind ARIH2. Instead, the data reveal an allosteric mechanism. NEDD8 uniquely contacts covalently linked CUL5, and elicits structural rearrangements that unveil cryptic ARIH2-binding sites. The data reveal how a ubiquitin-like protein induces protein-protein interactions indirectly, through allostery. Allosteric specificity of ubiquitin-like protein modifications may offer opportunities for therapeutic targeting.
History
DepositionMay 25, 2021-
Header (metadata) releaseSep 15, 2021-
Map releaseSep 15, 2021-
UpdateNov 6, 2024-
Current statusNov 6, 2024Processing site: PDBe / Status: Released

-
Structure visualization

Movie
  • Surface view with section colored by density value
  • Surface level: 0.0179
  • Imaged by UCSF Chimera
  • Download
  • Surface view colored by radius
  • Surface level: 0.0179
  • Imaged by UCSF Chimera
  • Download
  • Surface view with fitted model
  • Atomic models: PDB-7oni
  • Surface level: 0.0179
  • Imaged by UCSF Chimera
  • Download
Movie viewer
Structure viewerEM map:
SurfViewMolmilJmol/JSmol
Supplemental images

emd_12995.png

Downloads & links

-
Map

FileDownload / File: emd_12995.map.gz / Format: CCP4 / Size: 421.9 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 480 pix.
= 408.576 Å		0.85 Å/pix.
x 480 pix.
= 408.576 Å		0.85 Å/pix.
x 480 pix.
= 408.576 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: 0.0179 / Movie #1: 0.0179
Minimum - Maximum-0.025877394 - 0.08090484
Average (Standard dev.)0.000045745375 (±0.0010586332)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions480480480
Spacing480480480
CellA=B=C: 408.576 Å
α=β=γ: 90.0 °

CCP4 map header:

modeImage stored as Reals
Å/pix. X/Y/Z0.85120.85120.8512
M x/y/z480480480
origin x/y/z0.0000.0000.000
length x/y/z408.576408.576408.576
α/β/γ90.00090.00090.000
start NX/NY/NZ1331310
NX/NY/NZ223226424
MAP C/R/S123
start NC/NR/NS000
NC/NR/NS480480480
D min/max/mean-0.0260.0810.000

-
Supplemental data

-
Mask #1

Fileemd_12995_msk_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Additional map: #1

Fileemd_12995_additional_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: #2

Fileemd_12995_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: #1

Fileemd_12995_half_map_2.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Sample components

-
Entire : Neddylated CUL5 C-terminal region-RBX2-ARIH2

EntireName: Neddylated CUL5 C-terminal region-RBX2-ARIH2
Components
  • Complex: Neddylated CUL5 C-terminal region-RBX2-ARIH2
    • Protein or peptide: Cullin-5
    • Protein or peptide: E3 ubiquitin-protein ligase ARIH2
    • Protein or peptide: RING-box protein 2
    • Protein or peptide: NEDD8
  • Ligand: ZINC ION

-
Supramolecule #1: Neddylated CUL5 C-terminal region-RBX2-ARIH2

SupramoleculeName: Neddylated CUL5 C-terminal region-RBX2-ARIH2 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#4
Source (natural)Organism: Homo sapiens (human)

-
Macromolecule #1: Cullin-5

MacromoleculeName: Cullin-5 / type: protein_or_peptide / ID: 1 / 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 #2: E3 ubiquitin-protein ligase ARIH2

MacromoleculeName: E3 ubiquitin-protein ligase ARIH2 / type: protein_or_peptide / ID: 2 / Details: mutations : L381A E382A E455A / Number of copies: 1 / Enantiomer: LEVO / EC number: RBR-type E3 ubiquitin transferase
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 57.87982 KDa
Recombinant expressionOrganism: Escherichia coli 'BL21-Gold(DE3)pLysS AG' (bacteria)
SequenceString: GSMSVDMNSQ GSDSNEEDYD PNCEEEEEEE EDDPGDIEDY YVGVASDVEQ QGADAFDPEE YQFTCLTYKE SEGALNEHMT SLASVLKVS HSVAKLILVN FHWQVSEILD RYKSNSAQLL VEARVQPNPS KHVPTSHPPH HCAVCMQFVR KENLLSLACQ H QFCRSCWE ...String:
GSMSVDMNSQ GSDSNEEDYD PNCEEEEEEE EDDPGDIEDY YVGVASDVEQ QGADAFDPEE YQFTCLTYKE SEGALNEHMT SLASVLKVS HSVAKLILVN FHWQVSEILD RYKSNSAQLL VEARVQPNPS KHVPTSHPPH HCAVCMQFVR KENLLSLACQ H QFCRSCWE QHCSVLVKDG VGVGVSCMAQ DCPLRTPEDF VFPLLPNEEL REKYRRYLFR DYVESHYQLQ LCPGADCPMV IR VQEPRAR RVQCNRCNEV FCFKCRQMYH APTDCATIRK WLTKCADDSE TANYISAHTK DCPKCNICIE KNGGCNHMQC SKC KHDFCW MCLGDWKTHG SEYYECSRYK ENPDIVNQSQ QAQAREALKK YLFYFERWEN HNKSLQAAAQ TYQRIHEKIQ ERVM NNLGT WIDWQYLQNA AKLLAKCRYT LQYTYPYAYY MESGPRKKLF EYQQAQLEAE IANLSWKVER ADSYDRGDLE NQMHI AEQR RRTLLKDFHD T

UniProtKB: E3 ubiquitin-protein ligase ARIH2

-
Macromolecule #3: RING-box protein 2

MacromoleculeName: RING-box protein 2 / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 12.425073 KDa
Recombinant expressionOrganism: Trichoplusia ni (cabbage looper)
SequenceString:
GSEDGEETCA LASHSGSSGS KSGGDKMFSL KKWNAVAMWS WDVECDTCAI CRVQVMDACL RCQAENKQED CVVVWGECNH SFHNCCMSL WVKQNNRCPL CQQDWVVQRI GK

UniProtKB: RING-box protein 2

-
Macromolecule #4: NEDD8

MacromoleculeName: NEDD8 / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 9.230691 KDa
Recombinant expressionOrganism: Escherichia coli 'BL21-Gold(DE3)pLysS AG' (bacteria)
SequenceString:
GSMLIKVKTL TGKEIEIDIE PTDKVERIKE RVEEKEGIPP QQQRLIYSGK QMNDEKTAAD YKILGGSVLH LVLALRGGGG LRQ

UniProtKB: NEDD8

-
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

-
Electron microscopy

MicroscopeFEI TITAN KRIOS
Image recordingFilm or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 14.9 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

+
Image processing

Startup modelType of model: INSILICO MODEL
Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.4 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 191792
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: RELION (ver. 3.1.1)
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