[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

TitleIon coupling and inhibitory mechanisms of the human presynaptic high-affinity choline transporter CHT1.
Journal, issue, pagesStructure, Vol. 33, Issue 2, Page 321-329.e5, Year 2025
Publish dateFeb 6, 2025
AuthorsYunlong Qiu / Yiwei Gao / Qinru Bai / Yan Zhao /
PubMed AbstractIn cholinergic neurons, choline is the precursor of the excitatory neurotransmitter acetylcholine (ACh), which plays a fundamental role in the brain. The high-affinity choline transporter, CHT1, ...In cholinergic neurons, choline is the precursor of the excitatory neurotransmitter acetylcholine (ACh), which plays a fundamental role in the brain. The high-affinity choline transporter, CHT1, mediates the efficient recycling of choline to facilitate ACh synthesis in the presynapse. Here, we report high-resolution cryoelectron microscopic (cryo-EM) structures of CHT1 in complex with the inhibitors HC-3 and ML352, the substrate choline, and a substrate-free state. Our structures show distinct binding modes of the inhibitors with different chemical structures, revealing their inhibition mechanisms. Additionally, we observed a chloride ion that directly interacts with the substrate choline, thereby stabilizing its binding with CHT1. Two sodium ions, Na2 and Na3, were clearly identified, which we speculate might be involved in substrate binding and conformational transitions, respectively. Our structures provide molecular insights into the coupling mechanism of ion binding with substrate binding and conformational transitions, promoting our understanding of the ion-coupled substrate transport mechanism.
External linksStructure / PubMed:39657660
MethodsEM (single particle)
Resolution2.5 - 3.6 Å
Structure data

60386

8zqo

EMDB-60386, PDB-8zqo:
Human high-affinity choline transporter CHT1 bound to HC-3 under NaCl condition, with sodium and chloride ions coordinated.
Method: EM (single particle) / Resolution: 2.8 Å

60387

8zqp

EMDB-60387, PDB-8zqp:
Human high-affinity choline transporter CHT1 bound to ML352 under NaCl condition, with sodium ion coordinated.
Method: EM (single particle) / Resolution: 3.1 Å

60388

8zqq

EMDB-60388, PDB-8zqq:
Human high-affinity choline transporter CHT1 bound to choline under NaCl condition, with sodium and chloride ions coordinated.
Method: EM (single particle) / Resolution: 2.5 Å

60389

8zqr

EMDB-60389, PDB-8zqr:
Human high-affinity choline transporter CHT1 in apo state under NaCl condition.
Method: EM (single particle) / Resolution: 3.6 Å

Chemicals

ChemComp-NA:
Unknown entry

ChemComp-HC6:
(2S,2'S)-2,2'-biphenyl-4,4'-diylbis(2-hydroxy-4,4-dimethylmorpholin-4-ium)

ChemComp-CL:
Unknown entry

ChemComp-HOH:
WATER

PDB-1aow:
ANNEXIN IV

ChemComp-CHT:
CHOLINE ION

Source
  • homo sapiens (human)
KeywordsSTRUCTURAL PROTEIN / transporter / TRANSPORT PROTEIN

+
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