ArticleThe Journal of clinical investigation2008
Congenital myasthenia-related AChR delta subunit mutation interferes with intersubunit communication essential for channel gating.
Article in The Journal of clinical investigation, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 55 citations in OpenAlex.
- Congenital myasthenic syndromes.Orphanet journal of rare diseases · 2019Pooled it
- Clinical Variability and Genotype-Driven Outcomes in CHRND-Related Congenital Myasthenic Syndrome.European journal of neurology · 2026Article
- Slow-Channel Congenital Myasthenic Syndrome Due toJournal of clinical neurology (Seoul, Korea) · 2025Article
- Clinical and Pathologic Features of Congenital Myasthenic Syndromes Caused by 35 Genes-A Comprehensive Review.International journal of molecular sciences · 2023Review
- Origin of acetylcholine antagonism in ELIC, a bacterial pentameric ligand-gated ion channel.Communications biology · 2022Article
- Rare slow channel congenital myasthenic syndromes without repetitive compound muscle action potential and dramatic response to low dose fluoxetine.Acta neurologica Belgica · 2021Article
- Article
- Identification of a New QTL Region on Mouse Chromosome 1 Responsible for Male Hypofertility: Phenotype Characterization and Candidate Genes.International journal of molecular sciences · 2020Article
- Mutations causing congenital myasthenia reveal principal coupling pathway in the acetylcholine receptor ε-subunit.JCI insight · 2018Article
- Investigation of Congenital Myasthenia Reveals Functional Asymmetry of Invariant Acetylcholine Receptor (AChR) Cys-loop Aspartates.The Journal of biological chemistry · 2016Article
- Congenital myasthenic syndromes: pathogenesis, diagnosis, and treatment.The Lancet. Neurology · 2015Review
- Highly fatal fast-channel syndrome caused by AChR ε subunit mutation at the agonist binding site.Neurology · 2012Article
- Myasthenic syndrome AChRα C-loop mutant disrupts initiation of channel gating.The Journal of clinical investigation · 2012Article
- End-plate acetylcholine receptor: structure, mechanism, pharmacology, and disease.Physiological reviews · 2012Review
- Congenital myasthenic syndromes in 2012.Current neurology and neuroscience reports · 2012Review
- Current status of the congenital myasthenic syndromes.Neuromuscular disorders : NMD · 2012Review
- Altered plasmodial surface anion channel activity and in vitro resistance to permeating antimalarial compounds.Biochimica et biophysica acta · 2010Article
- What have we learned from the congenital myasthenic syndromes.Journal of molecular neuroscience : MN · 2010Review
- Functional and morphological evidence of age-related denervation in rat laryngeal muscles.The journals of gerontology. Series A, Biological sciences and medical sciences · 2009Article
- Further observations in congenital myasthenic syndromes.Annals of the New York Academy of Sciences · 2008Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Congenital myasthenias (CMs) arise from defects in neuromuscular junction-associated proteins. Deciphering the molecular bases of the CMs is required for therapy and illuminates structure-function relationships in these proteins. Here, we analyze the effects of a mutation in 1 of 4 homologous subunits in the AChR from a CM patient, a Leu to Pro mutation at position 42 of the delta subunit. The mutation is located in a region of contact between subunits required for rapid opening of the AChR channel and impedes the rate of channel opening. Substitutions of Gly, Lys, or Asp for deltaL42, or substitutions of Pro along the local protein chain, also slowed channel opening. Substitution of Pro for Leu in the epsilon subunit slowed opening, whereas this substitution had no effect in the beta subunit and actually sped opening in the alpha subunit. Analyses of energetic coupling between residues at the subunit interface showed that deltaL42 is functionally linked to alphaT127, a key residue in the adjacent alpha subunit required for rapid channel opening. Thus, deltaL42 is part of an intersubunit network that enables ACh binding to rapidly open the AChR channel, which may be compromised in patients with CM.
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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.