Extended Data Fig. 7: Titin-tail and tail-tail electrostatic interactions create the unique 3-crown repeat of myosin molecules in the C-zone (zoom for detail).

Myosin tails form extensive, mostly electrostatic, interactions with each other and with titin, which combined determine the axial and azimuthal positions of CrH, CrT, and CrD. a, b show representative examples. a, TaH and TaT (atomic models fitted into density map) run together in the S2 region (black rectangle) (Fig. 3), forming charge-charge interactions (right: red, negative; blue, positive), which shift CrT ~141 Å axially with respect to CrH (cf.²³; see also Extended Data Fig. 4). b, CrH tails also form electrostatic interactions with TA, involving all 11 domains of the 430 Å titin super-repeat (Fig. 4c). Interactions involve both proximal and distal S2 (bottom and top right, respectively), whose ~42 Å charge repeat²³ matches the ~42 Å spacing of the charged-surface titin domains. This is the most extensive titin-tail interaction in the reconstruction and is responsible for placing CrH crowns 430 Å apart, by matching them to the 430 Å length of the TA 11-domain super-repeat in its kinked conformation on the filament surface (Extended Data Fig. 6c). In summary, TaH-TA and TaH-TaT interactions (shown here), and TaD-TB interaction (Extended Data Fig. 6b), are the driving force for organizing the three crowns (CrH-CrT-CrD) in a quasi-helical arrangement in the human cardiac thick filament in the relaxed state.