[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

TitleSeesaw conformations of Npl4 in the human p97 complex and the inhibitory mechanism of a disulfiram derivative.
Journal, issue, pagesNat Commun, Vol. 12, Issue 1, Page 121, Year 2021
Publish dateJan 5, 2021
AuthorsMan Pan / Qingyun Zheng / Yuanyuan Yu / Huasong Ai / Yuan Xie / Xin Zeng / Chu Wang / Lei Liu / Minglei Zhao /
PubMed Abstractp97, also known as valosin-containing protein (VCP) or Cdc48, plays a central role in cellular protein homeostasis. Human p97 mutations are associated with several neurodegenerative diseases. ...p97, also known as valosin-containing protein (VCP) or Cdc48, plays a central role in cellular protein homeostasis. Human p97 mutations are associated with several neurodegenerative diseases. Targeting p97 and its cofactors is a strategy for cancer drug development. Despite significant structural insights into the fungal homolog Cdc48, little is known about how human p97 interacts with its cofactors. Recently, the anti-alcohol abuse drug disulfiram was found to target cancer through Npl4, a cofactor of p97, but the molecular mechanism remains elusive. Here, using single-particle cryo-electron microscopy (cryo-EM), we uncovered three Npl4 conformational states in complex with human p97 before ATP hydrolysis. The motion of Npl4 results from its zinc finger motifs interacting with the N domain of p97, which is essential for the unfolding activity of p97. In vitro and cell-based assays showed that the disulfiram derivative bis-(diethyldithiocarbamate)-copper (CuET) can bypass the copper transporter system and inhibit the function of p97 in the cytoplasm by releasing cupric ions under oxidative conditions, which disrupt the zinc finger motifs of Npl4, locking the essential conformational switch of the complex.
External linksNat Commun / PubMed:33402676 / PubMed Central
MethodsEM (single particle)
Resolution2.89 - 4.5 Å
Structure data

EMDB-21824:
Complex structure of human p97-Npl4/Ufd1 (State I)
Method: EM (single particle) / Resolution: 3.8 Å

EMDB-21825:
Complex structure of human p97-Npl4/Ufd1 (State II)
Method: EM (single particle) / Resolution: 3.7 Å

EMDB-21826:
Complex structure of human p97-Npl4/Ufd1 (State III)
Method: EM (single particle) / Resolution: 3.9 Å

EMDB-21827:
Human p97 in complex with Npl4/Ufd1 and polyubiquitinated Ub-Eos (State I)
Method: EM (single particle) / Resolution: 4.2 Å

EMDB-21828:
Human p97 in complex with Npl4/Ufd1 and polyubiquitinated Ub-Eos (State II)
Method: EM (single particle) / Resolution: 4.3 Å

EMDB-21829:
Human p97 in complex with Npl4/Ufd1 and polyubiquitinated Ub-Eos (State III)
Method: EM (single particle) / Resolution: 4.5 Å

EMDB-21830:
Complex of human p97-Npl4/Ufd1 in the presence of cupric ion
Method: EM (single particle) / Resolution: 3.5 Å

22521

7jy5

EMDB-22521: Map of human p97 in complex with ATPgammaS and Npl4/Ufd1 (masked around p97 and C6 averaged)
PDB-7jy5: Structure of human p97 in complex with ATPgammaS and Npl4/Ufd1 (masked around p97)
Method: EM (single particle) / Resolution: 2.89 Å

Chemicals

ChemComp-MG:
Unknown entry

ChemComp-AGS:
PHOSPHOTHIOPHOSPHORIC ACID-ADENYLATE ESTER / ATP-gamma-S, energy-carrying molecule analogue*YM

Source
  • homo sapiens (human)
KeywordsTRANSLOCASE / AAA+ ATPase Chaperon Protein homeostasis

+
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