[English] 日本語
Yorodumi
- EMDB-18345: Structure of the non-canonical CTLH E3 substrate receptor WDR26 b... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-18345
TitleStructure of the non-canonical CTLH E3 substrate receptor WDR26 bound to NMNAT1 substrate
Map data
Sample
  • Complex: Complex of human WDR26-CTLH E3 ligase bound to NMNAT1
    • Protein or peptide: Nicotinamide/nicotinic acid mononucleotide adenylyltransferase 1
    • Protein or peptide: WD repeat-containing protein 26
  • Ligand: BETA-NICOTINAMIDE RIBOSE MONOPHOSPHATE
  • Ligand: ZINC ION
KeywordsE3 ubiquitin ligase / CTLH / GID / NMNAT1 / YPEL5 / NAD / NADH / LIGASE
Function / homology
Function and homology information


negative regulation of apoptotic DNA fragmentation / protein ADP-ribosyltransferase-substrate adaptor activity / GID complex / nicotinamide-nucleotide adenylyltransferase / nicotinamide-nucleotide adenylyltransferase activity / nicotinate-nucleotide adenylyltransferase / nucleotide biosynthetic process / nicotinate-nucleotide adenylyltransferase activity / Nicotinate metabolism / ATP generation from poly-ADP-D-ribose ...negative regulation of apoptotic DNA fragmentation / protein ADP-ribosyltransferase-substrate adaptor activity / GID complex / nicotinamide-nucleotide adenylyltransferase / nicotinamide-nucleotide adenylyltransferase activity / nicotinate-nucleotide adenylyltransferase / nucleotide biosynthetic process / nicotinate-nucleotide adenylyltransferase activity / Nicotinate metabolism / ATP generation from poly-ADP-D-ribose / NAD biosynthetic process / ubiquitin ligase complex / Regulation of pyruvate metabolism / response to wounding / proteasome-mediated ubiquitin-dependent protein catabolic process / negative regulation of neuron apoptotic process / positive regulation of MAPK cascade / nuclear body / negative regulation of DNA-templated transcription / chromatin / mitochondrion / nucleoplasm / ATP binding / identical protein binding / nucleus / cytosol / cytoplasm
Similarity search - Function
: / Nicotinamide/nicotinate mononucleotide adenylyltransferase, eukaryotic / : / : / LisH-like dimerisation domain / Nicotinate/nicotinamide nucleotide adenylyltransferase / C-terminal to LisH motif. / CTLH, C-terminal LisH motif / C-terminal to LisH (CTLH) motif profile. / LIS1 homology (LisH) motif profile. ...: / Nicotinamide/nicotinate mononucleotide adenylyltransferase, eukaryotic / : / : / LisH-like dimerisation domain / Nicotinate/nicotinamide nucleotide adenylyltransferase / C-terminal to LisH motif. / CTLH, C-terminal LisH motif / C-terminal to LisH (CTLH) motif profile. / LIS1 homology (LisH) motif profile. / LIS1 homology motif / Cytidylyltransferase-like / Cytidyltransferase-like domain / Rossmann-like alpha/beta/alpha sandwich fold / Trp-Asp (WD) repeats profile. / Trp-Asp (WD) repeats circular profile. / WD domain, G-beta repeat / WD40 repeats / WD40 repeat / WD40-repeat-containing domain superfamily / WD40/YVTN repeat-like-containing domain superfamily
Similarity search - Domain/homology
WD repeat-containing protein 26 / Nicotinamide/nicotinic acid mononucleotide adenylyltransferase 1
Similarity search - Component
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.8 Å
AuthorsChrustowicz J / Sherpa D / Schulman BA
Funding support Germany, European Union, 3 items
OrganizationGrant numberCountry
Max Planck Society Germany
European Research Council (ERC)UPSmeetMet, 101098161European 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 30, 2023-
Header (metadata) releaseMay 15, 2024-
Map releaseMay 15, 2024-
UpdateJul 3, 2024-
Current statusJul 3, 2024Processing site: PDBe / Status: Released

-
Structure visualization

Supplemental images

emd_18345.png

Downloads & links

-
Map

FileDownload / File: emd_18345.map.gz / Format: CCP4 / Size: 83.7 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
1.44 Å/pix.
x 280 pix.
= 401.8 Å		1.44 Å/pix.
x 280 pix.
= 401.8 Å		1.44 Å/pix.
x 280 pix.
= 401.8 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 1.435 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.0321
Minimum - Maximum-0.056287065 - 0.12019871
Average (Standard dev.)0.00013647416 (±0.0023382471)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions280280280
Spacing280280280
CellA=B=C: 401.8 Å
α=β=γ: 90.0 °

-
Supplemental data

-
Mask #1

Fileemd_18345_msk_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Additional map: Map sharpened with DeepEMhancer

Fileemd_18345_additional_1.map
AnnotationMap sharpened with DeepEMhancer
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: #2

Fileemd_18345_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: #1

Fileemd_18345_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 NMNAT1

EntireName: Complex of human WDR26-CTLH E3 ligase bound to NMNAT1
Components
  • Complex: Complex of human WDR26-CTLH E3 ligase bound to NMNAT1
    • Protein or peptide: Nicotinamide/nicotinic acid mononucleotide adenylyltransferase 1
    • Protein or peptide: WD repeat-containing protein 26
  • Ligand: BETA-NICOTINAMIDE RIBOSE MONOPHOSPHATE
  • Ligand: ZINC ION

-
Supramolecule #1: Complex of human WDR26-CTLH E3 ligase bound to NMNAT1

SupramoleculeName: Complex of human WDR26-CTLH E3 ligase bound to NMNAT1 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#2
Details: Map obtained by focused refinement over NMNAT1-bound WDR26 dimer
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 1.1 MDa

-
Macromolecule #1: Nicotinamide/nicotinic acid mononucleotide adenylyltransferase 1

MacromoleculeName: Nicotinamide/nicotinic acid mononucleotide adenylyltransferase 1
type: protein_or_peptide / ID: 1 / Number of copies: 6 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 31.982502 KDa
Recombinant expressionOrganism: Escherichia coli (E. coli)
SequenceString: MENSEKTEVV LLACGSFNPI TNMHLRLFEL AKDYMNGTGR YTVVKGIISP VGDAYKKKGL IPAYHRVIMA ELATKNSKWV EVDTWESLQ KEWKETLKVL RHHQEKLEAS DCDHQQNSPT LERPGRKRKW TETQDSSQKK SLEPKTKAVP KVKLLCGADL L ESFAVPNL ...String:
MENSEKTEVV LLACGSFNPI TNMHLRLFEL AKDYMNGTGR YTVVKGIISP VGDAYKKKGL IPAYHRVIMA ELATKNSKWV EVDTWESLQ KEWKETLKVL RHHQEKLEAS DCDHQQNSPT LERPGRKRKW TETQDSSQKK SLEPKTKAVP KVKLLCGADL L ESFAVPNL WKSEDITQIV ANYGLICVTR AGNDAQKFIY ESDVLWKHRS NIHVVNEWIA NDISSTKIRR ALRRGQSIRY LV PDLVQEY IEKHNLYSSE SEDRNAGVIL APLQRNTAEA KT

UniProtKB: Nicotinamide/nicotinic acid mononucleotide adenylyltransferase 1

-
Macromolecule #2: WD repeat-containing protein 26

MacromoleculeName: WD repeat-containing protein 26 / type: protein_or_peptide / ID: 2 / 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, WD repeat-containing protein 26

-
Macromolecule #3: BETA-NICOTINAMIDE RIBOSE MONOPHOSPHATE

MacromoleculeName: BETA-NICOTINAMIDE RIBOSE MONOPHOSPHATE / type: ligand / ID: 3 / Number of copies: 2 / Formula: NMN
Molecular weightTheoretical: 335.227 Da
Chemical component information

ChemComp-NMN:
BETA-NICOTINAMIDE RIBOSE MONOPHOSPHATE

-
Macromolecule #4: ZINC ION

MacromoleculeName: ZINC ION / type: ligand / ID: 4 / Number of copies: 2 / 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
Image recordingFilm or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 71.4 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.3000000000000003 µm / Nominal defocus min: 0.8 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

+
Image processing

Startup modelType of model: EMDB MAP
EMDB ID:

12542

Final reconstructionApplied symmetry - Point group: C2 (2 fold cyclic) / Resolution.type: BY AUTHOR / Resolution: 3.8 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 5606
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