J. A. Spudich

Hypertrophic cardiomyopathy mutations Y115H and E497D disrupt the folded-back state of human beta-cardiac myosin allosterically

This study investigates how HCM mutations Y115H and E497D disrupt the folded-back state of human beta-cardiac myosin, leading to hypercontractility by destabilizing the OFF-state.

Structure of the Thin Filament in Human iPSC-derived Cardiomyocytes and its Response to Heart Disease

This study uses cryo-ET to analyze the structure of thin filaments in human iPSC-derived cardiomyocytes and how they change with disease-related perturbations.

Homologous mutations in β, embryonic, and perinatal muscle myosins have divergent effects on molecular power generation

This study compares the effects of homologous mutations in three muscle myosin isoforms, finding divergent molecular impacts that correlate with disease severity.

Cryo-EM structure of the folded-back state of human β-cardiac myosin

The paper reports the 3.6 Å cryo-EM structure of the folded-back IHM state of human β-cardiac myosin, revealing HCM mutation hotspots and structural differences from smooth muscle myosin IHMs.

Hypertrophic cardiomyopathy β-cardiac myosin mutation (P710R) leads to hypercontractility by disrupting super-relaxed state: multiscale measurements and computational modeling

This study investigates the P710R mutation in β-cardiac myosin, showing it causes hypercontractility by disrupting the super-relaxed state, using multiscale experiments and modeling.

Myosin motor domains carrying mutations implicated in early or late onset Hypertrophic Cardiomyopathy have similar properties

The paper analyzes myosin motor domain mutations in Hypertrophic Cardiomyopathy to compare early and late onset mutations, finding no clear functional differences but identifying distinct changes from DCM mutations.

The molecular basis of hypercontractility caused by the hypertrophic cardiomyopathy mutations R403Q and R663H

This study investigates how HCM mutations R403Q and R663H in myosin cause hypercontractility by increasing functionally-accessible myosin heads and affecting MyBP-C binding.

Hypertrophic cardiomyopathy mutations at the folded-back sequestered β-cardiac myosin S1-S2 and S1-S1 interfaces release sequestered heads and increase myosin enzymatic activity

This study shows HCM mutations at specific myosin interfaces increase accessible heads and myosin activity, contributing to hypercontractility.

Mavacamten stabilizes a folded-back sequestered super-relaxed state of β-cardiac myosin

The paper shows that mavacamten stabilizes a folded-back sequestered super-relaxed state of β-cardiac myosin, linking mutations to cardiomyopathy mechanisms.