[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

TitleReversible lipid-mediated pH-gating of connexin-46/50 by cryo-EM.
Journal, issue, pagesNat Commun, Year 2026
Publish dateJan 12, 2026
AuthorsJoshua M Jarodsky / Janette B Myers / Steve L Reichow /
PubMed AbstractGap junctions, formed by connexin proteins, establish direct electrical and metabolic coupling between cells, enabling coordinated tissue responses. These channels universally respond to ...Gap junctions, formed by connexin proteins, establish direct electrical and metabolic coupling between cells, enabling coordinated tissue responses. These channels universally respond to intracellular pH changes, closing under acidic conditions to limit the spread of cytotoxic signals during cellular stress, such as ischemia. Using cryo-electron microscopy (cryo-EM), we uncover insights into the structural mechanism of pH-gating in native lens connexin-46/50 (Cx46/50) gap junctions. Mild acidification drives lipid infiltration into the channel pore, displacing the N-terminal (NT) domain and stabilizing pore closure. Lipid involvement is shown to be both essential and fully reversible. Structural transitions involve an ensemble of gated states formed through non-cooperative NT domain movement as well as minor populations of a distinct destabilized open-state. These findings provide molecular insights into pH-gating dynamics, illustrating how structural changes may regulate gap junction function under cellular stress and linking Cx46/50 dysregulation to age-related cataract formation.
External linksNat Commun / PubMed:41526355
MethodsEM (single particle)
Resolution2.0 - 2.7 Å
Structure data

EMDB-73876: Stable open sheep connexin-46/50 in amphipol at low pH
PDB-9z7p: Stable open sheep connexin-46 in amphipol at low pH
PDB-9z7w: Stable open sheep connexin-50 in amphipol at low pH
Method: EM (single particle) / Resolution: 2.7 Å

EMDB-73885: Stable open state sheep connexin-46/50 in DMPC nanodiscs at neutral pH
PDB-9z81: Stable open state sheep connexin-46 in DMPC nanodiscs at neutral pH
PDB-9z82: Stable open state sheep connexin-50 in DMPC nanodiscs at neutral pH
Method: EM (single particle) / Resolution: 2.0 Å

EMDB-73896, PDB-9z8f:
Destabilized open state sheep connexin-46 in DMPC nanodiscs at neutral pH
PDB-9z8l: Destabilized open state sheep connexin-50 in DMPC nanodiscs at neutral pH
Method: EM (single particle) / Resolution: 2.2 Å

EMDB-73900: Gated state sheep connexin-46/50 in DMPC nanodiscs at neutral pH
PDB-9z8m: Gated state sheep connexin-46 in DMPC nanodiscs at neutral pH
PDB-9z9b: Gated state sheep connexin-50 in DMPC nanodiscs at neutral pH
Method: EM (single particle) / Resolution: 2.7 Å

EMDB-73942: Stable open state sheep connexin-46/50 in DMPC nanodiscs at low pH
PDB-9z9g: Stable open state sheep connexin-46 in DMPC nanodiscs at low pH
PDB-9z9h: Stable open state sheep connexin-50 in DMPC nanodiscs at low pH
Method: EM (single particle) / Resolution: 2.5 Å

EMDB-73957: Destabilized open state sheep connexin-46/50 in DMPC nanodiscs at low pH
PDB-9z9s: Destabilized open state sheep connexin-46 in DMPC nanodiscs at low pH
PDB-9z9w: Destabilized open state sheep connexin-50 in DMPC nanodiscs at low pH
Method: EM (single particle) / Resolution: 2.2 Å

EMDB-73962: Gated state sheep connexin-46/50 in DMPC nanodiscs at low pH
PDB-9z9x: Gated state sheep connexin-46 in DMPC nanodiscs at low pH
Method: EM (single particle) / Resolution: 2.3 Å

EMDB-73965: Asymmetrically gated state sheep connexin-46/50 in DMPC nanodiscs at low pH
PDB-9za3: Asymmetrically gated state sheep connexin-46 in DMPC nanodiscs at low pH
PDB-9za4: Asymmetrically gated state sheep connexin-50 in DMPC nanodiscs at low pH
Method: EM (single particle) / Resolution: 2.4 Å

PDB-9z9y:
Gated state sheep connexin-50 in DMPC nanodiscs at low pH
Method: ELECTRON MICROSCOPY / Resolution: 2.3 Å

Chemicals

ChemComp-MC3:
1,2-DIMYRISTOYL-RAC-GLYCERO-3-PHOSPHOCHOLINE / phospholipid*YM

ChemComp-HOH:
WATER

Source
  • ovis aries (sheep)
KeywordsMEMBRANE PROTEIN / connexin / gap junction / cryo-EM / pH regulation / lipid gating / large-pore channel

+
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