Allosteric destabilization of the super-relaxed state of cardiac myosin by hypertrophic cardiomyopathy-causing mutations

Abstract

Listen

Translate article

Hypertrophic cardiomyopathy (HCM), a leading cause of heart failure and sudden death, results from mutations in sarcomeric proteins. ∼35% of causative mutations affect β-cardiac myosin. It is now recognized that a large fraction of these may be affecting the conformational dynamics of myosin, and not its catalytic activity. Studies over the past decade have shifted the focus of HCM research to the evolutionarily conserved ‘super-relaxed’ (SRX) state of myosin, which is an important modulator of cardiac contractile output and energy consumption.