Molecular defects in cardiac myofilament Ca2+- regulation due to cardiomyopathy-linked mutations can be reversed by small molecules binding to troponin

Modulation of structure and dynamics of cardiac troponin by phosphorylation and mutations revealed by molecular dynamics simulations

“…The observation that an uncoupling mutation induces an opposite change in these metrics on phosphorylation supports this proposition. This could be further tested with other uncoupling mutations or small molecules that can reverse uncoupling36 ; it is noteworthy that most of the mutations in the troponin core that are reported to uncouple are at the interdomain interface (Supplementary figure6). Rigidification of the overall structure of troponin by mutations, mimicking phosphorylation, may explain how many different mutations in various components of the thin filament, can uncouple8 37 .…”