ArticleNature communications2020
Connexin-46/50 in a dynamic lipid environment resolved by CryoEM at 1.9 Å.
Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.
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Who cites it
69 citing papers in PubMed.
- Methods for the establishment of enzymatic mechanisms - from QM to ML.Chemical science · 2026Review
- Quantifying electrostatic control of docking and binding energetics in functional Cx36 gap junctions.Communications biology · 2026Article
- COeLife · 2026Article
- Lipids intercalate and mediate multi-channel assemblies of connexin-46/50 gap junctions.bioRxiv : the preprint server for biology · 2026Article
- Connexin 26 in Hearing Health and Disease: StructuralFoundations, Mutation Mechanisms, and Therapeutic Perspectives.International journal of molecular sciences · 2026Review
- Molecular Modeling and Dynamics of a Complete Connexin-43 Gap Junction Channel in Various Phosphorylation States.The journal of physical chemistry. B · 2026Article
- Reversible lipid-mediated pH-gating of connexin-46/50 by cryo-EM.Nature communications · 2026Article
- Connexin50 hemichannels are opened by COFrontiers in physiology · 2026Article
- Structural basis of PANX1 permeation and positive modulation by mefloquine.Nature communications · 2025Article
- Lipid dependence of connexin-32 gap junction channel conformations.Nature communications · 2025Article
- Mechanisms of permselectivity of connexin hemichannels to small molecules.The Journal of biological chemistry · 2025Article
- Cx47 Phosphorylation Exacerbates White Matter Damage and Kainic Acid Induced Epilepsy.CNS neuroscience & therapeutics · 2025Article
- Molecular dynamics simulation of GJC2 mutants reveal pathogenic mechanisms of PMLD1 and SPG44.The Journal of general physiology · 2025Article
- Single‑cell RNA sequencing reveals TMEM71 as an immunomodulatory biomarker predicting immune checkpoint blockade response in breast cancer.Discover oncology · 2025Article
- A large-scale curated and filterable dataset for cryo-EM foundation model pre-training.Scientific data · 2025Article
- Lipid probes to study ion channels.Current opinion in chemical biology · 2025Review
- Multiple carbamylation events are required for differential modulation of Cx26 hemichannels and gap junctions by COThe Journal of physiology · 2025Article
- Calcium induced N-terminal gating and pore collapse in connexin-46/50 gap junctions.bioRxiv : the preprint server for biology · 2025Article
- Deficiency in glutathione peroxidase 4 (GPX4) results in abnormal lens development and newborn cataract.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Mefloquine-induced conformational shift in Cx36 N-terminal helix leading to channel closure mediated by lipid bilayer.Nature communications · 2024Article
9 more citing papers are in PubMed but not listed here.
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8 authors.
Funding
Abstract
Gap junctions establish direct pathways for cells to transfer metabolic and electrical messages. The local lipid environment is known to affect the structure, stability and intercellular channel activity of gap junctions; however, the molecular basis for these effects remains unknown. Here, we incorporate native connexin-46/50 (Cx46/50) intercellular channels into a dual lipid nanodisc system, mimicking a native cell-to-cell junction. Structural characterization by CryoEM reveals a lipid-induced stabilization to the channel, resulting in a 3D reconstruction at 1.9 Å resolution. Together with all-atom molecular dynamics simulations, it is shown that Cx46/50 in turn imparts long-range stabilization to the dynamic local lipid environment that is specific to the extracellular lipid leaflet. In addition, ~400 water molecules are resolved in the CryoEM map, localized throughout the intercellular permeation pathway and contributing to the channel architecture. These results illustrate how the aqueous-lipid environment is integrated with the architectural stability, structure and function of gap junction communication channels.
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