Key result
Deletion of period 3 in tropomyosin reduced isometric tension to approximately 60% and significantly increased pCa50 (5.57 vs control 5.28), demonstrating its essential role in force generation.
Tropomyosin period 3 is essential for enhancing the interaction between actin and myosin and increasing isometric force in bovine myocardium.
Period 3 findings in bovine myocardium warrant human validation; leaves open therapeutic targeting in cardiomyopathy.
Tropomyosin (Tm) consists of 7 quasiequivalent repeats known as "periods," and its specific function may be associated with these periods. To test the hypothesis that either period 2 or 3 promotes force generation by inducing a positive allosteric effect on actin, we reconstituted the thin filament with mutant Tm in which either period 2 (Delta2Tm) or period 3 (Delta3Tm) was deleted. We then studied: isometric tension, stiffness, 6 kinetic constants, and the pCa-tension relationship. N-terminal acetylation of Tm did not cause any differences. The isometric tension in Delta2Tm remained unchanged, and was reduced to approximately 60% in Delta3Tm. Although the kinetic constants underwent small changes, the occupancy of strongly attached cross-bridges was not much different. The Hill factor (cooperativity) did not differ significantly between Delta2Tm (1.79 +/- 0.19) and the control (1.73 +/- 0.21), or Delta3Tm (1.35 +/- 0.22) and the control. In contrast, pCa(50) decreased slightly in Delta2Tm (5.11 +/- 0.07), and increased significantly in Delta3Tm (5.57 +/- 0.09) compared to the control (5.28 +/- 0.04). These results demonstrate that, when ions are present at physiological concentrations in the muscle fiber system, period 3 (but not period 2) is essential for the positive allosteric effect that enhances the interaction between actin and myosin, and increases isometric force of each cross-bridge.
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Kawai et al. (2009) studied this question. Deletion of period 2 (Delta2Tm) or period 3 (Delta3Tm) in mutant Tropomyosin vs. Control was evaluated on Isometric tension and pCa-tension relationship. Deletion of period 3 in tropomyosin reduced isometric tension to approximately 60% and significantly increased pCa50 (5.57 vs control 5.28), demonstrating its essential role in force generation.
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