ArticleBiophysical journal2012
Molecular dynamics simulations of the Cx26 hemichannel: insights into voltage-dependent loop-gating.
Article in Biophysical journal, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
What it found
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Who cites it
28 citing papers in PubMed.
- 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
- Expression of KID syndromic mutation Cx26S17F produces hyperactive hemichannels in supporting cells of the organ of Corti.Frontiers in cell and developmental biology · 2022Article
- Molecular mechanisms underlying enhanced hemichannel function of a cataract-associated Cx50 mutant.Biophysical journal · 2021Article
- Connexin-46/50 in a dynamic lipid environment resolved by CryoEM at 1.9 Å.Nature communications · 2020Article
- Microarray-based screening system identifies temperature-controlled activity of Connexin 26 that is distorted by mutations.Scientific reports · 2019Article
- Alterations in connexin 26 protein structure from lethal keratitis-ichthyosis-deafness syndrome mutations A88V and G45E.Journal of dermatological science · 2019Article
- The connexin26 human mutation N14K disrupts cytosolic intersubunit interactions and promotes channel opening.The Journal of general physiology · 2019Article
- Electrical coupling and its channels.The Journal of general physiology · 2018Review
- Article
- Calcium interactions with Cx26 hemmichannel: Spatial association between MD simulations biding sites and variant pathogenicity.Computational biology and chemistry · 2018Article
- Determining the molecular basis of voltage sensitivity in membrane proteins.The Journal of general physiology · 2018Article
- Gating of Connexin Channels by transjunctional-voltage: Conformations and models of open and closed states.Biochimica et biophysica acta. Biomembranes · 2018Review
- Structure of an innexin gap junction channel and cryo-EM sample preparation.Microscopy (Oxford, England) · 2017Review
- A structural and functional comparison of gap junction channels composed of connexins and innexins.Developmental neurobiology · 2017Review
- Accessing gap-junction channel structure-function relationships through molecular modeling and simulations.BMC cell biology · 2017Review
- Gap junction structure: unraveled, but not fully revealed.F1000Research · 2017Review
- Mechanism of gating by calcium in connexin hemichannels.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Structural studies of N-terminal mutants of Connexin 26 and Connexin 32 using (1)H NMR spectroscopy.Archives of biochemistry and biophysics · 2016Article
- Voltage regulation of connexin channel conductance.Yonsei medical journal · 2015Review
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
Loop-gating is one of two voltage-dependent mechanisms that regulate the open probability of connexin channels. The loop-gate permeability barrier is formed by a segment of the first extracellular loop (E1) (the parahelix) and appears to be accompanied by straightening of the bend angle between E1 and the first transmembrane domain (TM1). Here, all-atom molecular dynamics simulations are used to identify and characterize interacting van der Waals and electrostatic networks that stabilize the parahelices and TM1/E1 bend angles of the open Cx26 hemichannel. Dynamic fluctuations in an electrostatic network in each subunit are directly linked to the stability of parahelix structure and TM1/E1 bend angle in adjacent subunits. The electrostatic network includes charged residues that are pore-lining and thus positioned to be voltage sensors. We propose that the transition to the closed state is initiated by voltage-driven disruption of the networks that stabilize the open-state parahelix configuration, allowing the parahelix to protrude into the channel pore to form the loop-gate barrier. Straightening of the TM1/E1 bend appears to be a consequence of the reorganization of the interacting networks that accompany the conformational change of the parahelix. The electrostatic network extends across subunit boundaries, suggesting a concerted gating mechanism.
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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.