ArticleArchives of biochemistry and biophysics2016
The A31P missense mutation in cardiac myosin binding protein C alters protein structure but does not cause haploinsufficiency.
Article in Archives of biochemistry and biophysics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 23 citations in OpenAlex.
- The D75N and P161S Mutations in the C0-C2 Fragment of cMyBP-C Associated with Hypertrophic Cardiomyopathy Disturb the Thin Filament Activation, Nucleotide Exchange in Myosin, and Actin-Myosin Interaction.International journal of molecular sciences · 2024Article
- Cryo-electron tomography of intact cardiac muscle reveals myosin binding protein-C linking myosin and actin filaments.Journal of muscle research and cell motility · 2023Article
- Hypertrophic cardiomyopathy in purpose-bred cats with the A31P mutation in cardiac myosin binding protein-C.Scientific reports · 2023Article
- In situ FRET-based localization of the N terminus of myosin binding protein-C in heart muscle cells.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Assessment of the Contribution of a Thermodynamic and Mechanical Destabilization of Myosin-Binding Protein C Domain C2 to the Pathomechanism of Hypertrophic Cardiomyopathy-Causing Double MutationInternational journal of molecular sciences · 2021Article
- The Feline Cardiomyopathies: 2. Hypertrophic cardiomyopathy.Journal of feline medicine and surgery · 2021Article
- Protein haploinsufficiency drivers identify MYBPC3 variants that cause hypertrophic cardiomyopathy.The Journal of biological chemistry · 2021Article
- Nanomechanical Phenotypes in Cardiac Myosin-Binding Protein C Mutants That Cause Hypertrophic Cardiomyopathy.ACS nano · 2021Article
- Heat shock proteins and small nucleolar RNAs are dysregulated in a Drosophila model for feline hypertrophic cardiomyopathy.G3 (Bethesda, Md.) · 2021Article
- A Novel Homozygous Intronic Variant in TNNT2 Associates With Feline Cardiomyopathy.Frontiers in physiology · 2020Article
- Precision medicine validation: identifying theJournal of feline medicine and surgery · 2019Article
- Allelic imbalance and haploinsufficiency in MYBPC3-linked hypertrophic cardiomyopathy.Pflugers Archiv : European journal of physiology · 2019Review
- Inherited cardiomyopathies in veterinary medicine.Pflugers Archiv : European journal of physiology · 2019Review
- Investigations into the Sarcomeric Protein and CaFrontiers in physiology · 2017Article
- Myofilament modulation of contraction.Archives of biochemistry and biophysics · 2016Article
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Mutations in MYBPC3, the gene encoding cardiac myosin binding protein C (cMyBP-C), are a major cause of hypertrophic cardiomyopathy (HCM). While most mutations encode premature stop codons, missense mutations causing single amino acid substitutions are also common. Here we investigated effects of a single proline for alanine substitution at amino acid 31 (A31P) in the C0 domain of cMyBP-C, which was identified as a natural cause of HCM in cats. Results using recombinant proteins showed that the mutation disrupted C0 structure, altered sensitivity to trypsin digestion, and reduced recognition by an antibody that preferentially recognizes N-terminal domains of cMyBP-C. Western blots detecting A31P cMyBP-C in myocardium of cats heterozygous for the mutation showed a reduced amount of A31P mutant protein relative to wild-type cMyBP-C, but the total amount of cMyBP-C was not different in myocardium from cats with or without the A31P mutation indicating altered rates of synthesis/degradation of A31P cMyBP-C. Also, the mutant A31P cMyBP-C was properly localized in cardiac sarcomeres. These results indicate that reduced protein expression (haploinsufficiency) cannot account for effects of the A31P cMyBP-C mutation and instead suggest that the A31P mutation causes HCM through a poison polypeptide mechanism that disrupts cMyBP-C or myocyte function.
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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.