Key result
The E59D/D75Y double mutation in cardiac troponin C reduced the number of myosin S-1 binding sites on regulated thin filaments by approximately 23% (from 4.8 to 3.7 mol per mol filament).
Population
Cardiac muscle preparations and regulated thin filaments (RTF) expressing cardiac troponin C (CTnC) mutations
Comparison
E59D/D75Y double mutation in cardiac troponin C vs Wild type RTFs and single mutants (E59D or D75Y)
Design
Preclinical
Authors
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May underlie contractile impairment in E59D/D75Y cardiomyopathy; leaves open validation in human models.
Effect estimate: 23% reduction
Absolute Event Rate: 3.7% vs 4.8%
The E59D/D75Y mutation in cardiac troponin C likely causes dilated cardiomyopathy by altering thin filament conformation and reducing accessible myosin binding sites, thereby lowering contractile force.
Dweck et al. (2010) studied Dilated cardiomyopathy. E59D/D75Y double mutation in cardiac troponin C vs. Wild type cardiac troponin C was evaluated on Binding stoichiometry of myosin subfragment-1 (S-1) to regulated thin filaments (23% reduction). The E59D/D75Y double mutation in cardiac troponin C reduced the number of myosin S-1 binding sites on regulated thin filaments by approximately 23% (from 4.8 to 3.7 mol per mol filament).
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