[English] 日本語
Yorodumi Papers
- Database of articles cited by EMDB/PDB/SASBDB data -

+
Search query

Keywords
Structure methods
Author
Journal
IF

-
Structure paper

TitleNon-canonical substrate recognition by the human WDR26-CTLH E3 ligase regulates prodrug metabolism.
Journal, issue, pagesMol Cell, Vol. 84, Issue 10, Page 1948-1963.e11, Year 2024
Publish dateMay 16, 2024
AuthorsKarthik 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 /
PubMed AbstractThe 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.
External linksMol Cell / PubMed:38759627 / PubMed Central
MethodsEM (single particle)
Resolution3.2 - 13.9 Å
Structure data

EMDB-18170: YPEL5-bound WDR26-CTLH E3 ligase - assembly I
Method: EM (single particle) / Resolution: 8.9 Å

EMDB-18171: YPEL5-bound WDR26-CTLH E3 ligase - assembly II
Method: EM (single particle) / Resolution: 11.2 Å

EMDB-18172: NMNAT1 core-bound RANBP9-TWA1-WDR26 module of WDR26-CTLH E3 ligase
Method: EM (single particle) / Resolution: 4.7 Å

EMDB-18173: NMNAT1 loop-bound RANBP9-TWA1-WDR26 module of WDR26-CTLH E3 ligase
Method: EM (single particle) / Resolution: 8.7 Å

EMDB-18174: NMNAT1-bound WDR26-CTLH E3 ligase assembly I - class 1
Method: EM (single particle) / Resolution: 10.0 Å

EMDB-18175: NMNAT1-bound WDR26-CTLH E3 ligase assembly I - class 2
Method: EM (single particle) / Resolution: 10.3 Å

EMDB-18176: NMNAT1-bound WDR26-CTLH E3 ligase assembly II - class 1
Method: EM (single particle) / Resolution: 11.5 Å

EMDB-18177: NMNAT1-bound WDR26-CTLH E3 ligase assembly II - class 2
Method: EM (single particle) / Resolution: 13.9 Å

EMDB-18178: NMNAT1-bound WDR26-CTLH E3 ligase assembly II - class 3
Method: EM (single particle) / Resolution: 12.2 Å

18316

8qbn

EMDB-18316, PDB-8qbn:
Structure of the non-canonical CTLH E3 substrate receptor WDR26 bound to YPEL5
Method: EM (single particle) / Resolution: 3.2 Å

18345

8qe8

EMDB-18345, PDB-8qe8:
Structure of the non-canonical CTLH E3 substrate receptor WDR26 bound to NMNAT1 substrate
Method: EM (single particle) / Resolution: 3.8 Å

Chemicals

ChemComp-ZN:
Unknown entry

ChemComp-NMN:
BETA-NICOTINAMIDE RIBOSE MONOPHOSPHATE

Source
  • homo sapiens (human)
KeywordsLIGASE / E3 ubiquitin ligase / CTLH / GID / NMNAT1 / YPEL5 / NAD / NADH

+
About Yorodumi Papers

-
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 Papers

Database of articles cited by EMDB/PDB/SASBDB data

  • Database of articles cited by EMDB, PDB, and SASBDB entries
  • Using PubMed data

Related info.:EMDB / PDB / SASBDB / Yorodumi / EMN Papers / Changes in new EM Navigator and Yorodumi

Read more