Key result
The L348P gain-of-function mutation in the M-domain of cardiac myosin-binding protein-C significantly increased its binding affinity for actin and enhanced force activation independent of calcium.
Population
In vitro molecular model studying the M-domain of cardiac myosin-binding protein-C (cMyBP-C)
Comparison
Site-directed mutagenesis of charged residues… vs Wild-type or unmutated M-domain
Design
Preclinical
Authors
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M-domain mutations may refine HCM variant classification; leaves open whether they alter clinical phenotypes or guide therapy.
Absolute Event Rate: 3.2% vs 7.4%
p-value: p=<0.05
The tri-helix bundle of the cMyBP-C M-domain is crucial for regulating cardiac muscle contraction via actin binding, and its mutation can lead to functional changes associated with hypertrophic cardiomyopathy.
Bezold et al. (2013) studied Hypertrophic cardiomyopathy (context). L348P mutation in the M-domain of cMyBP-C vs. Wild-type C1C2 protein was evaluated on Actin binding affinity (Kd in μM) (p=<0.05). The L348P gain-of-function mutation in the M-domain of cardiac myosin-binding protein-C significantly increased its binding affinity for actin and enhanced force activation independent of calcium.
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