Figure 4. Titin functions as a template for myosin organization (zoom for detail).

a, Density map showing one pair of titin strands (TA, orange Fn domains, purple Ig domains; TB, yellow Fn, purple Ig). The two titins run nearly parallel except in the middle region (Ig-Fn-Fn-Fn) of each super-repeat (Fig. 2c, d, ED Fig. 6). b, Same as a, but including myosin molecules CrD (red), CrH (green) and CrT (blue), to show organization of tails with respect to titins. c, Titins form extensive interactions with myosin tails in a sector (ED Fig. 2e), creating and strengthening the tail network. Interactions of TB and TA with individual tails from CrD, CrH and CrT (TaD, TaH and TaT, respectively) are shown. Numbers indicate the individual titin domains involved. TaH interacts with both TB and TA: the first half (S2) extensively with TA, the second half (LMM) with TB. TaT interacts only (and minimally) with TA, mainly in its S2 region, and then travels towards the filament core (Fig. 3), with no further interaction with either titin. TaD (mainly S2) interacts with TB, mostly in the mid-region (Ig-Fn-Fn-Fn) of two super-repeats (T5–T8 and T15–T18), but not with TA. d, TB and TA from adjacent sectors interact with each other to create a complete, 3-sector, filament. The main interaction, at T7/T8, is electrostatic (left, atomic model fitted into EM map; right, surface charge interaction). e, Representative example of titin-tail interface, showing TA (T9–T11) interaction with two TaH’s from different crowns and a TaT. Fitting of tail and titin atomic models into the map suggests β-β hairpin loops in Ig and Fn domains mostly form the titin-tail interface (left, black boxes). A single titin domain can interact with as many as 3 myosin tails originating from different crowns (right, inset). See also ED Fig. 6 and Supplementary Video 5.