ArticleCell reports2020
A Steric "Ball-and-Chain" Mechanism for pH-Mediated Regulation of Gap Junction Channels.
Article in Cell reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 59 citations in OpenAlex.
- Connexin 26 in Hearing Health and Disease: StructuralFoundations, Mutation Mechanisms, and Therapeutic Perspectives.International journal of molecular sciences · 2026Review
- In situ structure of the human gap junction.Science advances · 2026Article
- Metabolic starvation-induced cell swelling drives solid stress in tumors.bioRxiv : the preprint server for biology · 2026Article
- Reversible lipid-mediated pH-gating of connexin-46/50 by cryo-EM.Nature communications · 2026Article
- Calcium induced N-terminal gating and pore collapse in connexin-46/50 gap junctions.bioRxiv : the preprint server for biology · 2025Article
- Computation suggests that the cell adhesion sub-proteome is enriched for sites of pH-dependence and charge burial.PloS one · 2025Article
- DiffModeler: large macromolecular structure modeling for cryo-EM maps using a diffusion model.Nature methods · 2024Article
- Large-pore connexin hemichannels function like molecule transporters independent of ion conduction.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Article
- Connexin Gap Junction Channels and Hemichannels: Insights from High-Resolution Structures.Biology · 2024Review
- Simulation of gap junction formation reveals critical role of Cys disulfide redox state in connexin hemichannel docking.Cell communication and signaling : CCS · 2024Article
- DiffModeler: Large Macromolecular Structure Modeling in Low-Resolution Cryo-EM Maps Using Diffusion Model.bioRxiv : the preprint server for biology · 2024Article
- Structures of wild-type and selected CMT1X mutant connexin 32 gap junction channels and hemichannels.Science advances · 2023Article
- Article
- The intercalated disc: a unique organelle for electromechanical synchrony in cardiomyocytes.Physiological reviews · 2023Review
- Cryo-EM structures of human Cx36/GJD2 neuronal gap junction channel.Nature communications · 2023Article
- Conformational changes in the human Cx43/GJA1 gap junction channel visualized using cryo-EM.Nature communications · 2023Article
- The Multifaceted Role of Connexins in Tumor Microenvironment Initiation and Maintenance.Biology · 2023Review
- Simulation-predicted and -explained inheritance model of pathogenicity confirmed by transgenic mice models.Computational and structural biotechnology journal · 2023Article
- The Hydrophobic Residues in Amino Terminal Domains of Cx46 and Cx50 Are Important for Their Gap Junction Channel Ion Permeation and Gating.International journal of molecular sciences · 2022Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Gap junction channels (GJCs) mediate intercellular communication and are gated by numerous conditions such as pH. The electron cryomicroscopy (cryo-EM) structure of Cx26 GJC at physiological pH recapitulates previous GJC structures in lipid bilayers. At pH 6.4, we identify two conformational states, one resembling the open physiological-pH structure and a closed conformation that displays six threads of density, that join to form a pore-occluding density. Crosslinking and hydrogen-deuterium exchange mass spectrometry reveal closer association between the N-terminal (NT) domains and the cytoplasmic loops (CL) at acidic pH. Previous electrophysiologic studies suggest an association between NT residue N14 and H100 near M2, which may trigger the observed movement of M2 toward M1 in our cryo-EM maps, thereby accounting for additional NT-CL crosslinks at acidic pH. We propose that these pH-induced interactions and conformational changes result in extension, ordering, and association of the acetylated NT domains to form a hexameric "ball-and-chain" gating particle.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.