ArticleJournal of biomolecular structure & dynamics2012
Permeation pathway of homomeric connexin 26 and connexin 30 channels investigated by molecular dynamics.
Article in Journal of biomolecular structure & dynamics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 60 citations in OpenAlex.
- Direct connexin-26 interactions with membrane proteins functionally relevant to the cochlea.Human genetics · 2025Article
- Model-based evaluation of connexin hemichannel permeability.Computational and structural biotechnology journal · 2025Article
- An Ala/Glu difference in E1 of Cx26 and Cx30 contributes to their differential anionic permeabilities.The Journal of general physiology · 2024Article
- A pore locus in the E1 domain differentially regulates Cx26 and Cx30 hemichannel function.The Journal of general physiology · 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
- Calcium Regulation of Connexin Hemichannels.International journal of molecular sciences · 2024Review
- Molecular Dynamics Simulation of Permeation Through Connexin Channels.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Functional Consequences of Pathogenic Variants of theBiomolecules · 2023Review
- Divergence between Hemichannel and Gap Junction Permeabilities of Connexin 30 and 26.Life (Basel, Switzerland) · 2023Article
- A Quantitative Assay for CaInternational journal of molecular sciences · 2022Article
- Connexons Coupling to Gap Junction Channel: Potential Role for Extracellular Protein Stabilization Centers.Biomolecules · 2021Article
- Lens Connexin Channels Show Differential Permeability to Signaling Molecules.International journal of molecular sciences · 2020Review
- Connexin-46/50 in a dynamic lipid environment resolved by CryoEM at 1.9 Å.Nature communications · 2020Article
- Structural determinants underlying permeant discrimination of the Cx43 hemichannel.The Journal of biological chemistry · 2019Article
- The Effects of Calcium on Lipid-Protein Interactions and Ion Flux in the Cx26 Connexon Embedded into a POPC Bilayer.The Journal of membrane biology · 2019Article
- Magnesium interactions with a CX26 connexon in lipid bilayers.Journal of molecular modeling · 2019Article
- Inner Ear Connexin Channels: Roles in Development and Maintenance of Cochlear Function.Cold Spring Harbor perspectives in medicine · 2019Review
- A Human-Derived Monoclonal Antibody Targeting Extracellular Connexin Domain Selectively Modulates Hemichannel Function.Frontiers in physiology · 2019Article
- Article
- Calcium interactions with Cx26 hemmichannel: Spatial association between MD simulations biding sites and variant pathogenicity.Computational biology and chemistry · 2018Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Mutations in the genes GJB2 and GJB6 encoding human connnexin26 (hCx26) and connexin30 (hCx30), respectively, are the leading cause of non-syndromic prelingual deafness in several human populations. In this work, we exploited the high degree (77%) of sequence similarity shared by hCx26 and hCx30 to create atomistic models of homomeric hCx26 and hCx30 connexons starting from the X-ray crystallographic structure of an intercellular channel formed by hCx26 protomers at 3.5-å resolution. The equilibrium dynamics of the two protein complexes was followed for 40 ns each by Molecular Dynamics (MD) simulations. Our results indicate that, in hCx26, positively charged Lys41 residues establish a potential barrier within the fully open channel, hindering ion diffusion in the absence of an electrochemical gradient. A similar role is played, in hCx30, by negatively charged Glu49 residues. The different position and charge of these two ion sieves account for the differences in unitary conductance observed experimentally. Our results are discussed in terms of present models of voltage gating in connexin channels.
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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.