Interplay between the overlapping ends of tropomyosin and the N terminus of cardiac troponin T affects tropomyosin states on actin

The functional significance of the molecular swivel at the head‐to‐tail overlapping ends of contiguous tropomyosin (Tm) dimers in striated muscle is unknown. Contractile measurements were made in muscle fibers from transgenic (TG) mouse hearts that expressed a mutant α‐Tm (Tm H276N ). We also reconstituted mouse cardiac troponin T (McTnT) N‐terminal deletion mutants, McTnT 1–44Δ and McTnT 45–74Δ , into muscle fibers from Tm H276N . For controls, we used the wild‐type (WT) McTnT because altered effects could be correlated with the mutant forms of McTnT. Tm H276N slowed crossbridge (XB) detachment rate ( g ) by 19%. McTnT 1‐44Δ attenuated Ca 2+ ‐activated maximal tension against Tm WT (36%) and Tm H276N (38%), but sped g only against Tm H276N by 35%. The rate of tension redevelopment decreased (17%) only in McTnT 1–44Δ + Tm H276N fibers. McTnT 45–74Δ attenuated tension (19%) and myofilament Ca 2+ sensitivity (pCa 50 =5.93 vs. 6.00 in the control fibers) against Tm H276N , but not against Tm WT background. Thus, altered XB cycling kinetics decreased the fraction of strongly bound XBs in McTnT 1‐44Δ + Tm H276N fibers, whereas diminished thin‐filament cooperativity attenuated tension in McTnT 45‐74Δ + Tm H276N fibers. In summary, our study is the first to show that the interplay between the N terminus of cTnT and the overlapping ends of contiguous Tm effectuates different states of Tm on the actin filament. —Mamidi, R., Michael, J. J., Muthuchamy, M., Chandra, M., Interplay between the overlapping ends of tropomyosin and the N terminus of cardiac troponin T affects tropomyosin states on actin. FASEB J. 27, 3848–3859 (2013). www.fasebj.org