[English] 日本語
Yorodumi
- EMDB-18316: Structure of the non-canonical CTLH E3 substrate receptor WDR26 b... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-18316
TitleStructure of the non-canonical CTLH E3 substrate receptor WDR26 bound to YPEL5
Map data
Sample
  • Complex: Complex of human WDR26-CTLH E3 ligase bound to YPEL5
    • Protein or peptide: WD repeat-containing protein 26
    • Protein or peptide: Protein yippee-like 5
  • Ligand: ZINC ION
KeywordsE3 ubiquitin ligase / CTLH / GID / NMNAT1 / YPEL5 / LIGASE
Function / homology
Function and homology information


GID complex / mitotic spindle pole / ubiquitin ligase complex / tertiary granule lumen / midbody / proteasome-mediated ubiquitin-dependent protein catabolic process / cell population proliferation / ficolin-1-rich granule lumen / centrosome / Neutrophil degranulation ...GID complex / mitotic spindle pole / ubiquitin ligase complex / tertiary granule lumen / midbody / proteasome-mediated ubiquitin-dependent protein catabolic process / cell population proliferation / ficolin-1-rich granule lumen / centrosome / Neutrophil degranulation / mitochondrion / extracellular region / nucleoplasm / metal ion binding / nucleus / cytosol / cytoplasm
Similarity search - Function
Yippee domain / Yippee family / Yippee domain profile. / LisH-like dimerisation domain / C-terminal to LisH motif. / CTLH, C-terminal LisH motif / C-terminal to LisH (CTLH) motif profile. / Yippee/Mis18/Cereblon / Yippee zinc-binding/DNA-binding /Mis18, centromere assembly / LIS1 homology (LisH) motif profile. ...Yippee domain / Yippee family / Yippee domain profile. / LisH-like dimerisation domain / C-terminal to LisH motif. / CTLH, C-terminal LisH motif / C-terminal to LisH (CTLH) motif profile. / Yippee/Mis18/Cereblon / Yippee zinc-binding/DNA-binding /Mis18, centromere assembly / LIS1 homology (LisH) motif profile. / LIS1 homology motif / WD domain, G-beta repeat / WD40 repeats / WD40 repeat / Trp-Asp (WD) repeats profile. / Trp-Asp (WD) repeats circular profile. / WD40-repeat-containing domain superfamily / WD40/YVTN repeat-like-containing domain superfamily
Similarity search - Domain/homology
Protein yippee-like 5 / WD repeat-containing protein 26
Similarity search - Component
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.2 Å
AuthorsChrustowicz J / Sherpa D / Schulman BA
Funding support Germany, European Union, 3 items
OrganizationGrant numberCountry
Max Planck Society Germany
European Research Council (ERC)H2020 789016-NEDD8ActivateEuropean Union
German Research Foundation (DFG)SCHU 3196/1-1 Germany
CitationJournal: Mol Cell / Year: 2024
Title: Non-canonical substrate recognition by the human WDR26-CTLH E3 ligase regulates prodrug metabolism.
Authors: Karthik V Gottemukkala / Jakub Chrustowicz / Dawafuti Sherpa / Sara Sepic / Duc Tung Vu / Özge Karayel / Eleftheria C Papadopoulou / Annette Gross / Kenji Schorpp / Susanne von Gronau / ...Authors: Karthik V Gottemukkala / Jakub Chrustowicz / Dawafuti Sherpa / Sara Sepic / Duc Tung Vu / Özge Karayel / Eleftheria C Papadopoulou / Annette Gross / Kenji Schorpp / Susanne von Gronau / Kamyar Hadian / Peter J Murray / Matthias Mann / Brenda A Schulman / Arno F Alpi /
Abstract: The yeast glucose-induced degradation-deficient (GID) E3 ubiquitin ligase forms a suite of complexes with interchangeable receptors that selectively recruit N-terminal degron motifs of metabolic ...The yeast glucose-induced degradation-deficient (GID) E3 ubiquitin ligase forms a suite of complexes with interchangeable receptors that selectively recruit N-terminal degron motifs of metabolic enzyme substrates. The orthologous higher eukaryotic C-terminal to LisH (CTLH) E3 complex has been proposed to also recognize substrates through an alternative subunit, WDR26, which promotes the formation of supramolecular CTLH E3 assemblies. Here, we discover that human WDR26 binds the metabolic enzyme nicotinamide/nicotinic-acid-mononucleotide-adenylyltransferase 1 (NMNAT1) and mediates its CTLH E3-dependent ubiquitylation independently of canonical GID/CTLH E3-family substrate receptors. The CTLH subunit YPEL5 inhibits NMNAT1 ubiquitylation and cellular turnover by WDR26-CTLH E3, thereby affecting NMNAT1-mediated metabolic activation and cytotoxicity of the prodrug tiazofurin. Cryoelectron microscopy (cryo-EM) structures of NMNAT1- and YPEL5-bound WDR26-CTLH E3 complexes reveal an internal basic degron motif of NMNAT1 essential for targeting by WDR26-CTLH E3 and degron mimicry by YPEL5's N terminus antagonizing substrate binding. Thus, our data provide a mechanistic understanding of how YPEL5-WDR26-CTLH E3 acts as a modulator of NMNAT1-dependent metabolism.
History
DepositionAug 24, 2023-
Header (metadata) releaseMay 15, 2024-
Map releaseMay 15, 2024-
UpdateMay 29, 2024-
Current statusMay 29, 2024Processing site: PDBe / Status: Released

-
Structure visualization

Supplemental images

emd_18316.png

Downloads & links

-
Map

FileDownload / File: emd_18316.map.gz / Format: CCP4 / Size: 91.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Voxel sizeX=Y=Z: 1.395 Å
Density
Contour LevelBy AUTHOR: 0.0483
Minimum - Maximum-0.15324624 - 0.31817102
Average (Standard dev.)0.00011945298 (±0.003690284)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions288288288
Spacing288288288
CellA=B=C: 401.76 Å
α=β=γ: 90.0 °

-
Supplemental data

-
Mask #1

Fileemd_18316_msk_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Additional map: Map sharpened with DeepEMhancer

Fileemd_18316_additional_1.map
AnnotationMap sharpened with DeepEMhancer
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: #2

Fileemd_18316_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: #1

Fileemd_18316_half_map_2.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Sample components

-
Entire : Complex of human WDR26-CTLH E3 ligase bound to YPEL5

EntireName: Complex of human WDR26-CTLH E3 ligase bound to YPEL5
Components
  • Complex: Complex of human WDR26-CTLH E3 ligase bound to YPEL5
    • Protein or peptide: WD repeat-containing protein 26
    • Protein or peptide: Protein yippee-like 5
  • Ligand: ZINC ION

-
Supramolecule #1: Complex of human WDR26-CTLH E3 ligase bound to YPEL5

SupramoleculeName: Complex of human WDR26-CTLH E3 ligase bound to YPEL5 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#2
Details: Map obtained by focused refinement over YPEL5-bound WDR26 dimer
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 900 KDa

-
Macromolecule #1: WD repeat-containing protein 26

MacromoleculeName: WD repeat-containing protein 26 / type: protein_or_peptide / ID: 1 / Number of copies: 2 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 70.539773 KDa
Recombinant expressionOrganism: Trichoplusia ni (cabbage looper)
SequenceString: MQANGAGGGG GGGGGGGGGG GGGGGQGQTP ELACLSAQNG ESSPSSSSSA GDLAHANGLL PSAPSAASNN SNSLNVNNGV PGGAAAASS ATVAAASATT AASSSLATPE LGSSLKKKKR LSQSDEDVIR LIGQHLNGLG LNQTVDLLMQ ESGCRLEHPS A TKFRNHVM ...String:
MQANGAGGGG GGGGGGGGGG GGGGGQGQTP ELACLSAQNG ESSPSSSSSA GDLAHANGLL PSAPSAASNN SNSLNVNNGV PGGAAAASS ATVAAASATT AASSSLATPE LGSSLKKKKR LSQSDEDVIR LIGQHLNGLG LNQTVDLLMQ ESGCRLEHPS A TKFRNHVM EGDWDKAEND LNELKPLVHS PHAIVRMKFL LLQQKYLEYL EDGKVLEALQ VLRCELTPLK YNTERIHVLS GY LMCSHAE DLRAKAEWEG KGTASRSKLL DKLQTYLPPS VMLPPRRLQT LLRQAVELQR DRCLYHNTKL DNNLDSVSLL IDH VCSRRQ FPCYTQQILT EHCNEVWFCK FSNDGTKLAT GSKDTTVIIW QVDPDTHLLK LLKTLEGHAY GVSYIAWSPD DNYL VACGP DDCSELWLWN VQTGELRTKM SQSHEDSLTS VAWNPDGKRF VTGGQRGQFY QCDLDGNLLD SWEGVRVQCL WCLSD GKTV LASDTHQRIR GYNFEDLTDR NIVQEDHPIM SFTISKNGRL ALLNVATQGV HLWDLQDRVL VRKYQGVTQG FYTIHS CFG GHNEDFIASG SEDHKVYIWH KRSELPIAEL TGHTRTVNCV SWNPQIPSMM ASASDDGTVR IWGPAPFIDH QNIEEEC SS MDS

UniProtKB: WD repeat-containing protein 26

-
Macromolecule #2: Protein yippee-like 5

MacromoleculeName: Protein yippee-like 5 / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 13.860658 KDa
Recombinant expressionOrganism: Trichoplusia ni (cabbage looper)
SequenceString:
MGRIFLDHIG GTRLFSCANC DTILTNRSEL ISTRFTGATG RAFLFNKVVN LQYSEVQDRV MLTGRHMVRD VSCKNCNSKL GWIYEFATE DSQRYKEGRV ILERALVRES EGFEEHVPSD NS

UniProtKB: Protein yippee-like 5

-
Macromolecule #3: ZINC ION

MacromoleculeName: ZINC ION / type: ligand / ID: 3 / Number of copies: 3 / 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
DetailsSample mixed with 0.01% beta-OG right before plunging

-
Electron microscopy

MicroscopeFEI TITAN KRIOS
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy / Nominal defocus max: 2.3000000000000003 µm / Nominal defocus min: 0.8 µm
Image recordingFilm or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 71.2 e/Å2
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

-
Image processing

Startup modelType of model: EMDB MAP
EMDB ID:

12542

Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD
Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.2 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 77172
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