Key result
TnT1 increased the apparent cooperative unit size of Tm.actin from 6 to 9, while TnT2IC reduced the S1-binding rate constant 2-3-fold in the absence of Ca2+.
The N- and C-terminal regions of troponin T act independently to modulate myosin S1 binding to the tropomyosin-actin thin filament, contributing to muscle regulation.
Does not support clinical translation; leaves open independent troponin T domain effects on thin filament regulation in vivo.
Mild proteolytic cleavage of the troponin complex yields TnT1, the N-terminal fragment of troponin T, and TnT2IC, a complex of the C-terminal fragment of troponin T (TnT2) with troponin I (TnI) and troponin C (TnC) [Morris, E. P., & Lehrer, S. S. (1984) Biochemistry 23, 2214-2220]. Both TnT1 and TnT2IC bind tightly to the tropomyosin.actin (Tm.actin) thin filament and influence the interaction of myosin subfragment 1 (S1) with Tm.actin. TnT1 does not affect the rate of S1 binding to Tm.actin but does increase the cooperativity with which S1 "turns on" Tm.actin, monitored by the excimer fluorescence of a pyrene label attached to Cys 190 of Tm [Geeves, M.A., & Lehrer, S. S. (1994) Biophys. J. 67, 273-282]. The apparent cooperative unit size of Tm.actin is increased from 6 to 9 by TnT1 and to 12 by whole troponin. In contrast, TnT2IC has no effect on the cooperativity of Tm.actin but does make the apparent S1-binding rate constant, kapp, Ca(2+)-sensitive; i.e., in the absence of Ca2+, kapp is reduced 2-3-fold by both TnT2IC and whole troponin. Thus, the N- and C-terminal regions of TnT appear to act independently in modulating effects of S1 binding to the Tm.actin thin filament that are important in regulation.
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Schaertl et al. (1995) studied this question. TnT1 and TnT2IC vs. Whole troponin was evaluated on Cooperativity and S1-binding rate constant to Tm.actin. TnT1 increased the apparent cooperative unit size of Tm.actin from 6 to 9, while TnT2IC reduced the S1-binding rate constant 2-3-fold in the absence of Ca2+.
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