ArticleThe Journal of biological chemistry2009
A Two-amino Acid Mutation Encountered in Duchenne Muscular Dystrophy Decreases Stability of the Rod Domain 23 (R23) Spectrin-like Repeat of Dystrophin.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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23 citing papers in PubMed, 36 citations in OpenAlex.
- Weak protein-bicelle binding quantification via surface-based DNA nanolevers.European biophysics journal : EBJ · 2026Article
- DMD-Associated Dilated Cardiomyopathy: Genotypes, Phenotypes, and Phenocopies.Circulation. Genomic and precision medicine · 2023Article
- Cardiomyopathy-associated variants alter the structure and function of the α-actinin-2 actin-binding domain.Biochemical and biophysical research communications · 2023Article
- Increased Actin Binding Is a Shared Molecular Consequence of Numerous SCA5 Mutations in β-III-Spectrin.Cells · 2023Article
- De Novo and Dominantly Inherited SPTAN1 Mutations Cause Spastic Paraplegia and Cerebellar Ataxia.Movement disorders : official journal of the Movement Disorder Society · 2022Article
- Combining Protein Expression and Molecular Data Improves Mutation Characterization of Dystrophinopathies.Frontiers in neurology · 2021Article
- Structural basis for high-affinity actin binding revealed by a β-III-spectrin SCA5 missense mutation.Nature communications · 2017Article
- β-III-spectrin spinocerebellar ataxia type 5 mutation reveals a dominant cytoskeletal mechanism that underlies dendritic arborization.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- IgA Structure Variations Associate with Immune Stimulations and IgA Mesangial Deposition.Journal of the American Society of Nephrology : JASN · 2016Article
- A human β-III-spectrin spinocerebellar ataxia type 5 mutation causes high-affinity F-actin binding.Scientific reports · 2016Article
- Disease-proportional proteasomal degradation of missense dystrophins.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- DMD Mutations in 576 Dystrophinopathy Families: A Step Forward in Genotype-Phenotype Correlations.PloS one · 2015Article
- In vitro stability of therapeutically relevant, internally truncated dystrophins.Skeletal muscle · 2015Article
- Dystrophin insufficiency causes selective muscle histopathology and loss of dystrophin-glycoprotein complex assembly in pig skeletal muscle.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2014Article
- Article
- Thermal stability of chicken brain α-spectrin repeat 17: a spectroscopic study.Journal of biomolecular NMR · 2012Article
- Novel mutation in spectrin-like repeat 1 of dystrophin central domain causes protein misfolding and mild Becker muscular dystrophy.The Journal of biological chemistry · 2012Article
- Thermodynamic stability, unfolding kinetics, and aggregation of the N-terminal actin-binding domains of utrophin and dystrophin.Proteins · 2012Article
- The crystal structures of dystrophin and utrophin spectrin repeats: implications for domain boundaries.PloS one · 2012Article
- Spectrin-like repeats 11-15 of human dystrophin show adaptations to a lipidic environment.The Journal of biological chemistry · 2011Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Lack of functional dystrophin causes severe Duchenne muscular dystrophy. The subsarcolemmal location of dystrophin, as well as its association with both cytoskeleton and membrane, suggests a role in the mechanical regulation of muscular membrane stress. In particular, phenotype rescue in a Duchenne muscular dystrophy mice model has shown that some parts of the central rod domain of dystrophin, constituted by 24 spectrin-like repeats, are essential. In this study, we made use of rare missense pathogenic mutations in the dystrophin gene and analyzed the biochemical properties of the isolated repeat 23 bearing single or double mutations E2910V and N2912D found in muscle dystrophy with severity grading. No dramatic effect on secondary and tertiary structure of the repeat was found in mutants compared with wild type as revealed by circular dichroism and NMR. Thermal and chemical unfolding data from circular dichroism and tryptophan fluorescence show significant decrease of stability for the mutants, and stopped-flow spectroscopy shows decreased refolding rates. The most deleterious single mutation is the N2912D replacement, although we observe additive effects of the two mutations on repeat stability. Based on three-dimensional structures built by homology molecular modeling, we discuss the modifications of the mutation-induced repeat stability. We conclude that the main forces involved in repeat stability are electrostatic inter-helix interactions that are disrupted following mutations. This study represents the first analysis at the protein level of the consequences of missense mutations in the human dystrophin rod domain. Our results suggest that it may participate in mechanical weakening of dystrophin-deficient muscle.
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