ArticleBiochemistry2012
Long-range effects of familial hypertrophic cardiomyopathy mutations E180G and D175N on the properties of tropomyosin.
Article in Biochemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 44 citations in OpenAlex.
- Functional and Structural Properties of Cytoplasmic Tropomyosin Isoforms Tpm1.8 and Tpm1.9.International journal of molecular sciences · 2024Article
- Novel Mutation Glu98Lys in Cardiac Tropomyosin Alters Its Structure and Impairs Myocardial Relaxation.International journal of molecular sciences · 2023Article
- Thin filament cardiomyopathies: A review of genetics, disease mechanisms, and emerging therapeutics.Frontiers in cardiovascular medicine · 2022Review
- Loss of crossbridge inhibition drives pathological cardiac hypertrophy in patients harboring the TPM1 E192K mutation.The Journal of general physiology · 2021Article
- Impact of A134 and E218 Amino Acid Residues of Tropomyosin on Its Flexibility and Function.International journal of molecular sciences · 2020Article
- Functional outcomes of structural peculiarities of striated muscle tropomyosin.Journal of muscle research and cell motility · 2020Review
- Thin filament dysfunctions caused by mutations in tropomyosin Tpm3.12 and Tpm1.1.Journal of muscle research and cell motility · 2020Review
- Cardiomyopathy-associated mutations in tropomyosin differently affect actin-myosin interaction at single-molecule and ensemble levels.Journal of muscle research and cell motility · 2019Review
- Moving beyond simple answers to complex disorders in sarcomeric cardiomyopathies: the role of integrated systems.Pflugers Archiv : European journal of physiology · 2019Review
- Functional significance of HCM mutants of tropomyosin, V95A and D175N, studied withBiophysics and physicobiology · 2019Article
- Temperature sensitive point mutations in fission yeast tropomyosin have long range effects on the stability and function of the actin-tropomyosin copolymer.Biochemical and biophysical research communications · 2018Article
- Fropofol decreases force development in cardiac muscle.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2018Article
- Structural and Dynamic Properties of Allergen and Non-Allergen Forms of Tropomyosin.Structure (London, England : 1993) · 2018Article
- HCM and DCM cardiomyopathy-linked α-tropomyosin mutations influence off-state stability and crossbridge interaction on thin filaments.Archives of biochemistry and biophysics · 2018Article
- Pathogenesis of Hypertrophic Cardiomyopathy is Mutation Rather Than Disease Specific: A Comparison of the Cardiac Troponin T E163R and R92Q Mouse Models.Journal of the American Heart Association · 2017Article
- The Relaxation Properties of Myofibrils Are Compromised by Amino Acids that Stabilize α-Tropomyosin.Biophysical journal · 2017Article
- Investigating the effects of tropomyosin mutations on its flexibility and interactions with filamentous actin using molecular dynamics simulation.Journal of muscle research and cell motility · 2016Article
- N-acetylcysteine reverses diastolic dysfunction and hypertrophy in familial hypertrophic cardiomyopathy.American journal of physiology. Heart and circulatory physiology · 2015Article
- Tropomyosin dynamics.Journal of muscle research and cell motility · 2014Review
- The myosin-activated thin filament regulatory state, M⁻-open: a link to hypertrophic cardiomyopathy (HCM).Journal of muscle research and cell motility · 2014Review
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
Cardiac α-tropomyosin (Tm) single-site mutations D175N and E180G cause familial hypertrophic cardiomyopathy (FHC). Previous studies have shown that these mutations increase both Ca(2+) sensitivity and residual contractile activity at low Ca(2+) concentrations, which causes incomplete relaxation during diastole resulting in hypertrophy and sarcomeric disarray. However, the molecular basis for the cause and the difference in the severity of the manifested phenotypes of disease are not known. In this work we have (1) used ATPase studies using reconstituted thin filaments in solution to show that these FHC mutants result in an increase in Ca(2+) sensitivity and an increased residual level of ATPase, (2) shown that both FHC mutants increase the rate of cleavage at R133, ~45 residues N-terminal to the mutations, when free and bound to actin, (3) shown that for Tm-E180G, the increase in the rate of cleavage is greater than that for D175N, and (4) shown that for E180G, cleavage also occurs at a new site 53 residues C-terminal to E180G, in parallel with cleavage at R133. The long-range decreases in dynamic stability due to these two single-site mutations suggest increases in flexibility that may weaken the ability of Tm to inhibit activity at low Ca(2+) concentrations for D175N and to a greater degree for E180G, which may contribute to differences in the severity of FHC.
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Registered trials
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