ArticleFrontiers in physiology2014
Molecular dynamics simulations highlight structural and functional alterations in deafness-related M34T mutation of connexin 26.
Article in Frontiers in physiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
20 citing papers in PubMed, 34 citations in OpenAlex.
- Connexin 26 in Hearing Health and Disease: StructuralFoundations, Mutation Mechanisms, and Therapeutic Perspectives.International journal of molecular sciences · 2026Review
- Expanding genotype-phenotype correlation of Kenny-Caffey syndrome type 1.Clinical and experimental pediatrics · 2025Article
- Molecular Dynamics Simulation of Permeation Through Connexin Channels.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Functional Consequences of Pathogenic Variants of theBiomolecules · 2023Review
- Simulation-predicted and -explained inheritance model of pathogenicity confirmed by transgenic mice models.Computational and structural biotechnology journal · 2023Article
- Role of salt-bridging interactions in recognition of viral RNA by arginine-rich peptides.Biophysical journal · 2021Article
- Connexin 46 and connexin 50 gap junction channel properties are shaped by structural and dynamic features of their N-terminal domains.The Journal of physiology · 2021Article
- Structural determinants underlying permeant discrimination of the Cx43 hemichannel.The Journal of biological chemistry · 2019Article
- Inner Ear Connexin Channels: Roles in Development and Maintenance of Cochlear Function.Cold Spring Harbor perspectives in medicine · 2019Review
- Calcium interactions with Cx26 hemmichannel: Spatial association between MD simulations biding sites and variant pathogenicity.Computational biology and chemistry · 2018Article
- Cues to Opening Mechanisms FromFrontiers in molecular neuroscience · 2018Article
- 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
- DFNB1 Non-syndromic Hearing Impairment: Diversity of Mutations and Associated Phenotypes.Frontiers in molecular neuroscience · 2017Review
- Modulation of Asymmetric Flux in Heterotypic Gap Junctions by Pore Shape, Particle Size and Charge.Frontiers in physiology · 2017Article
- Computational Studies of Molecular Permeation through Connexin26 Channels.Biophysical journal · 2016Article
- Tryptophan Scanning Reveals Dense Packing of Connexin Transmembrane Domains in Gap Junction Channels Composed of Connexin32.The Journal of biological chemistry · 2015Article
- The p.Cys169Tyr variant of connexin 26 is not a polymorphism.Human molecular genetics · 2015Article
- Structure-function correlation analysis of connexin50 missense mutations causing congenital cataract: electrostatic potential alteration could determine intracellular trafficking fate of mutants.BioMed research international · 2014Article
- Study of Met34Thr variant in nonsyndromic hearing loss in four Portuguese families.Porto biomedical journalArticle
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Mutations of the GJB2 gene encoding the connexin 26 (Cx26) gap junction protein, which is widely expressed in the inner ear, are the primary cause of hereditary non-syndromic hearing loss in several populations. The deafness-associated single amino acid substitution of methionine 34 (M34) in the first transmembrane helix (TM1) with a threonine (T) ensues in the production of mutant Cx26M34T channels that are correctly synthesized and assembled in the plasma membrane. However, mutant channels overexpressed in HeLa cells retain only 11% of the wild type unitary conductance. Here we extend and rationalize those findings by comparing wild type Cx26 (Cx26WT) and Cx26M34T mutant channels in silico, using molecular dynamics simulations. Our results indicate that the quaternary structure of the Cx26M34T hemichannel is altered at the level of the pore funnel due to the disruption of the hydrophobic interaction between M34 and tryptophan 3 (W3) in the N-terminal helix (NTH). Our simulations also show that external force stimuli applied to the NTHs can detach them from the inner wall of the pore more readily in the mutant than in the wild type hemichannel. These structural alterations significantly increase the free energy barrier encountered by permeating ions, correspondingly decreasing the unitary conductance of the Cx26M34T hemichannel. Our results accord with the proposal that the mutant resides most of the time in a low conductance state. However, the small displacement of the NTHs in our Cx26M34T hemichannel model is not compatible with the formation of a pore plug as in the related Cx26M34A mutant.
Indexed as
Identifiers
What OpenQuestion holds
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.