Molecular Structure Analysis of Troponin-C to Study Muscle Contractile Control Mechanism.

The relative sliding movement between myosin and actin filaments is controlled by the troponin, which consists of three subunits called troponin-I, troponin-T, and troponin-C. Troponin-I inhibits this sliding movement, and troponin-C suppresses this inhibitory function under the calcium-ion binding state. In this paper, we investigate the function of troponin-C using the molecular mechanics analysis code "AMBER". The molecular structure data of troponin-C are provided by Sundaralingain et. al. [Science, 227(1985), 945-948]. Conformations in four cases, e.g., without Ca2+, with two Ca2+ in high-affinity site, with two Ca2+ in low-affinity site, and with four Ca2+, are determined by molecular mechanics analysis. The r. m. S. fluctuations and the isothermal compressibilities are evaluated by normal mode analyses and compared at N-domain, C-domain, D/E-helix, and troponin-C itself. Isothermal compressibility reveals the flexibility and the functional ability of troponin C. It is demonstrated that only when Ca2+ binds in low-affinity site does the D/E-helix twist very much and consequently, N-domain and C-domain approach each other. Our results reveals how Ca2+ induces troponin-C activation and it might concern to the kinetic function of troponin-C.