Fig. 8.

Proposed mechanism on how cTnT-I79N variant increases DRX myosin population. The cTnT-I79N variant destabilizes the interaction between TnT1 loop and actin, leading to thin-filament disinhibition at low Ca²⁺ levels (Fig. 1). Under normal physiological circumstances, a few ON (DRX) heads are checking the thin filaments and will be close enough to be electrostatically attracted to actin-binding sites. As ON (DRX) state heads are being pulled out of the DRX head pool by binding to actin, this might be expected to shift the OFF (SRX)/ON (DRX) equilibrium toward the ON state, facilitating subsequent crossbridge formation and force generation, even at low Ca²⁺.