The thin filament actin interfaces relevant to contractile regulation. (A) The thin and thick filament interaction interfaces include the myosin motor domains (which adopt DRX, SRX, and crossbridge conformations) and cMyBP-C. Therapeutic agents and mutations linked to HCM have been shown to modify the population of crossbridges in the SRX and DRX. Illustrated here is Mava, which leads to an increased population of SRX myosin motor domains from a DRX population, whereas OM leads to an increased population in DRX together with a prolongation of crossbridge duty cycle. (B) The Ca²⁺-dependent conformational transitions in the cTn complex illustrate the cTnI inhibitory peptide (IP; yellow, aa 138–149), the switch peptide (SwP; magenta, aa 150–161), and the mobile domain (MD; red, aa 162–210). (C) The cooperative spread of activation between neighbor Tn-Tm units increases cTnC binding affinity for Ca²⁺. See text for further discussion. ELC, essential LC.