ArticleThe Journal of biological chemistry2013
Cardiomyopathy mutations in the tail of β-cardiac myosin modify the coiled-coil structure and affect integration into thick filaments in muscle sarcomeres in adult cardiomyocytes.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 39 citations in OpenAlex.
- Thick filament molecular interfaces play a critical role in the pathogenesis of hypertrophic cardiomyopathy.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- The role of MEGF10 in myoblast fusion and hypertrophic response to overload of skeletal muscle.Journal of muscle research and cell motility · 2025Article
- Investigation of mutation spectrum amongst patients with familial primary cardiomyopathy using targeted NGS in Indian population.Journal of applied genetics · 2024Article
- Article
- Myosin folding boosts solubility in cardiac muscle sarcomeres.JCI insight · 2024Article
- Visualization of cardiac thick filament dynamics in ex vivo heart preparations.Journal of molecular and cellular cardiology · 2023Article
- Article
- Introducing and Implementing Genetic Assessment in Cardio-Obstetrics Clinical Practice: Clinical and Genetic Workup of Patients with Cardiomyopathy.International journal of molecular sciences · 2023Article
- Evaluation of the DBA/2J mouse as a potential background strain for genetic models of cardiomyopathy.Journal of molecular and cellular cardiology plus · 2022Article
- Genetic Insights into Primary Restrictive Cardiomyopathy.Journal of clinical medicine · 2022Review
- Cardiac sarcomere mechanics in health and disease.Biophysical reviews · 2021Review
- Secondary Structure of the Novel Myosin Binding Domain WYR and Implications within Myosin Structure.Biology · 2021Article
- Actin Mutations and Their Role in Disease.International journal of molecular sciences · 2020Review
- Real-time visualization of titin dynamics reveals extensive reversible photobleaching in human induced pluripotent stem cell-derived cardiomyocytes.American journal of physiology. Cell physiology · 2020Article
- A1603P and K1617del, Mutations in β-Cardiac Myosin Heavy Chain that Cause Laing Early-Onset Distal Myopathy, Affect Secondary Structure and Filament Formation In Vitro and In Vivo.Journal of molecular biology · 2018Article
- Hypertrophic Cardiomyopathy: Genetics, Pathogenesis, Clinical Manifestations, Diagnosis, and Therapy.Circulation research · 2017Review
- Tropomyosin 1: Multiple roles in the developing heart and in the formation of congenital heart defects.Journal of molecular and cellular cardiology · 2017Article
- Characterization of long and stable de novo single alpha-helix domains provides novel insight into their stability.Scientific reports · 2017Article
- Impact of MYH6 variants in hypoplastic left heart syndrome.Physiological genomics · 2016Article
- Hypertrophic cardiomyopathy mutations in the calponin-homology domain of ACTN2 affect actin binding and cardiomyocyte Z-disc incorporation.The Biochemical journal · 2016Article
Corrections and comments
- Erratum issued
Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
It is unclear why mutations in the filament-forming tail of myosin heavy chain (MHC) cause hypertrophic or dilated cardiomyopathy as these mutations should not directly affect contraction. To investigate this, we first investigated the impact of five hypertrophic cardiomyopathy-causing (N1327K, E1356K, R1382W, E1555K, and R1768K) and one dilated cardiomyopathy-causing (R1500W) tail mutations on their ability to incorporate into muscle sarcomeres in vivo. We used adenoviral delivery to express full-length wild type or mutant enhanced GFP-MHC in isolated adult cardiomyocytes. Three mutations (N1327K, E1356K, and E1555K) reduced enhanced GFP-MHC incorporation into muscle sarcomeres, whereas the remainder had no effect. No mutations significantly affected contraction. Fluorescence recovery after photobleaching showed that fluorescence recovery for the mutation that incorporated least well (N1327K) was significantly faster than that of WT with half-times of 25.1 ± 1.8 and 32.2 ± 2.5 min (mean ± S.E.), respectively. Next, we determined the effects of each mutation on the helical properties of wild type and seven mutant peptides (7, 11, or 15 heptads long) from the myosin tail by circular dichroism. R1382W and E1768K slightly increased the α-helical nature of peptides. The remaining mutations reduced α-helical content, with N1327K showing the greatest reduction. Only peptides containing residues 1301-1329 were highly α-helical suggesting that this region helps in initiation of coiled coil. These results suggest that small effects of mutations on helicity translate into a reduced ability to incorporate into sarcomeres, which may elicit compensatory hypertrophy.
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