Panel A shows the standard longitudinal arrangement of sarcomere proteins starting from the M-band (pink) and moving through the P-zone (green), C-zone (light blue), and D-zone (tan) toward the I/A junction (purple). The protein layers are labeled from top to bottom as My B P-C, Myosin, Titin beta, and Titin alpha. In the C-zone, the diagram displays eleven distinct segments labeled C-zone 11 through C-zone 6. A key feature identified in the Titin beta strand within the C-zone 11 region is a beta loop, which is indicated by a black vertical arrow. The Titin alpha and beta strands consist of alternating white and purple oval subunits, which align precisely with the myosin heads and My B P-C structures. Panel B illustrates the structural alterations caused by the Titin Delta A164-167 mutation. While the overall zones (M-band, P-zone, C-zone, D-zone) remain, the Titin strands show a physical deformity labeled as a kink located in the C-zone 11 segment. This kink replaces the smooth loop structure seen in the wild-type and appears as a sharp upward and downward displacement of the Titin strands. Due to the deletion of the four specific exons, the segments of the C-zone are shifted toward the M-band. This shift is highlighted by dashed blue lines connecting the wild-type segments to the mutant segments, showing that the mutant C-zone 5 is now pulled into the visible frame where C-zone 6 was previously located. Additionally, the P-zone width (indicated by a green double-headed arrow) is significantly shorter in the mutant compared to the wild-type.
Proposed model of the WT (A) and TtnΔA164–167 (B) thick filament. (A and B) The thick filament components (titin, myosin, and cMyBP-C) are shown vertically stacked for clarity (labels to the right). The myosin molecules in the P-zone (P1, P2, P3) are orange, and the myosin molecules in the C-zone are peach. Ig domains of titin and cMyBP-C are magenta, FnIII domains are white, and titin’s kinase domain is indigo. The deletion of titin domains A164–167 shifts titin’s P-zone toward the M-band and results in a kinked titin conformation in titin’s C-zone 11-domain super-repeats. All other titin C-zone repeats moved 43 nm closer toward the M-band and are correctly phased with myosin and cMyBP-C. The shift in location from WT to TtnΔA164–167 is marked by dotted lines corresponding to the color of the zone.