[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

TitleStructural insights into the activation of TMEM175 by small molecule.
Journal, issue, pagesNeuron, Vol. 113, Issue 21, Page 3567-33581.e9, Year 2025
Publish dateNov 5, 2025
AuthorsXuewu Zhu / Meixuan Ping / Heng Liu / Ting Yu / Zhongwen Jiang / Zhenhua Liu / Chanjing Li / Xinjiao Hou / Qinyu Chu / Shuyao Li / Caiwen Mao / Ting Luo / Chunlan Kang / Feng Wang / Chuanyan Yang / Meiqin Tang / Zhidong Jiang / Zhaobing Gao / Hong Liu / H Eric Xu / Beisha Tang / Xi Cheng / Wanchao Yin / Yu Zhou / Ping Li /
PubMed AbstractThe upregulation of transmembrane protein 175 (TMEM175) has the potential to improve Parkinson's disease (PD) by aiding in the removal of α-synuclein aggregates. Understanding the structural basis ...The upregulation of transmembrane protein 175 (TMEM175) has the potential to improve Parkinson's disease (PD) by aiding in the removal of α-synuclein aggregates. Understanding the structural basis of TMEM175 agonisms is crucial for uncovering its therapeutic potential for PD. Here, we have identified the first cryo-electron microscopy (cryo-EM) structure of human TMEM175 complexes with three agonists: DCY1020, DCY1040, and TUG-891. An open state of TMEM175 is unequivocally captured, laying the groundwork for designing more effective agonists. Further investigations using surface plasmon resonance, systematic mutagenesis, whole-endolysosome patch-clamp techniques, and molecular dynamics simulations consistently revealed that DCY1020/1040 binds at the interface between two subunits, inducing an open conformation further augmented by the synergistic agonist TUG-891. Notably, these agonists facilitate the removal of pathological α-synuclein and restore functions of PD-related TMEM175 variants in neurons. Our findings provide proof of concept that drug discovery targeting TMEM175 can develop agonists capable of effectively reducing pathological α-synuclein levels in PD.
External linksNeuron / PubMed:40865534
MethodsEM (single particle)
Resolution2.74 - 3.4 Å
Structure data

65303

9vsp

EMDB-65303, PDB-9vsp:
The DCY1020-bound structure of TMEM175
Method: EM (single particle) / Resolution: 3.4 Å

65304

9vsq

EMDB-65304, PDB-9vsq:
The TUG-891-bound structure of TMEM175
Method: EM (single particle) / Resolution: 2.74 Å

65305

9vsr

EMDB-65305, PDB-9vsr:
The DCY1040 and TUG-891-bound structure of TMEM175
Method: EM (single particle) / Resolution: 2.92 Å

Chemicals


PDB Unreleased entry

PDB-1etd: Unknown entry

ChemComp-YN9:
3-{4-[(4-fluoro-4'-methyl[1,1'-biphenyl]-2-yl)methoxy]phenyl}propanoic acid

ChemComp-CLR:
CHOLESTEROL

ChemComp-K:
Unknown entry

ChemComp-HOH:
WATER

PDB-1ete:
CRYSTAL STRUCTURE OF THE FLT3 LIGAND

Source
  • homo sapiens (human)
KeywordsMEMBRANE PROTEIN / TMEM175 / cro-EM / agonist / Parkinson / lysosome / TUG-891

+
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