ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2009
Main immunogenic region structure promotes binding of conformation-dependent myasthenia gravis autoantibodies, nicotinic acetylcholine receptor conformation maturation, and agonist sensitivity.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 90 citations in OpenAlex.
- MuSK IgG4 autoantibodies cause myasthenia gravis by inhibiting binding between MuSK and Lrp4.Proceedings of the National Academy of Sciences of the United States of America · 2013Trial
- Genome-wide analysis reveals pathways important for the development and maturation of excitatory synaptic connections to GABAergic neurons.G3 (Bethesda, Md.) · 2026Article
- Application analysis of transfected cell method for detecting AChR antibodies in MG patients.Scientific reports · 2026Article
- Beyond the Surface: Investigating the Potential Mechanisms of Non-Motor Symptoms in Myasthenia Gravis.European journal of neurology · 2025Review
- Composition and function of AChR chimeric autoantibody receptor T cells for antigen-specific B cell depletion in myasthenia gravis.Science advances · 2025Article
- Concordance between radioimmunoassay and fixed cell-based assay in subjects without myasthenia gravis: optimizing the diagnostic approach.European journal of neurology · 2024Article
- Myasthenia gravis: the changing treatment landscape in the era of molecular therapies.Nature reviews. Neurology · 2024Review
- An original potentiating mechanism revealed by the cryo-EM structures of the human α7 nicotinic receptor in complex with nanobodies.Nature communications · 2023Article
- Clinicoserological insights into patients with immune checkpoint inhibitor-induced myasthenia gravis.Annals of clinical and translational neurology · 2023Article
- Delineating the activity of the potent nicotinic acetylcholine receptor agonists (+)-anatoxin-a and (-)-hosieine-A.Acta crystallographica. Section F, Structural biology communications · 2022Article
- Myasthenia gravis-specific aberrant neuromuscular gene expression by medullary thymic epithelial cells in thymoma.Nature communications · 2022Article
- Autoantibody of NRIP, a novel AChR-interacting protein, plays a detrimental role in myasthenia gravis.Journal of cachexia, sarcopenia and muscle · 2021Article
- In Silico Studies of Lamiaceae Diterpenes with Bioinsecticide Potential againstMolecules (Basel, Switzerland) · 2021Article
- Possible implications of dysregulated nicotinic acetylcholine receptor diffusion and nanocluster formation in myasthenia gravis.Neural regeneration research · 2021Review
- A Functional Human-on-a-Chip Autoimmune Disease Model of Myasthenia Gravis for Development of Therapeutics.Frontiers in cell and developmental biology · 2021Article
- Article
- Generation of anti-idiotypic antibodies to detect anti-spacer antibody idiotopes in acute thrombotic thrombocytopenic purpura patients.Haematologica · 2019Article
- Antigen Extraction and B Cell Activation Enable Identification of Rare Membrane Antigen Specific Human B Cells.Frontiers in immunology · 2019Article
- Multiple regions in the extracellular domain of the glycine receptor determine receptor activity.The Journal of biological chemistry · 2018Article
- Structural insights into the molecular mechanisms of myasthenia gravis and their therapeutic implications.eLife · 2017Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
The main immunogenic region (MIR) is a conformation-dependent region at the extracellular apex of alpha1 subunits of muscle nicotinic acetylcholine receptor (AChR) that is the target of half or more of the autoantibodies to muscle AChRs in human myasthenia gravis and rat experimental autoimmune myasthenia gravis. By making chimeras of human alpha1 subunits with alpha7 subunits, both MIR epitopes recognized by rat mAbs and by the patient-derived human mAb 637 to the MIR were determined to consist of two discontiguous sequences, which are adjacent only in the native conformation. The MIR, including loop alpha1 67-76 in combination with the N-terminal alpha helix alpha1 1-14, conferred high-affinity binding for most rat mAbs to the MIR. However, an additional sequence corresponding to alpha1 15-32 was required for high-affinity binding of human mAb 637. A water soluble chimera of Aplysia acetylcholine binding protein with the same alpha1 MIR sequences substituted was recognized by a majority of human, feline, and canine myasthenia gravis sera. The presence of the alpha1 MIR sequences in alpha1/alpha7 chimeras greatly promoted AChR expression and significantly altered the sensitivity to activation. This reveals a structural and functional, as well as antigenic, significance of the MIR.
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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.