Indexing metadata

A number of point mutations has been identified in the genes of contractile and regulatory proteins of skeletal muscle that can lead to dysfunction of muscle tissue. The molecular mechanisms of muscle contraction in the presence of mutant muscle proteins in the sarcomere remain poorly understood. In the current study, we examined the impact of the glutamate-to-alanine substitution at position 150 (Glu150Ala) of γ-tropomyosin associated with cap disease and fiber-type disproportion in humans on the molecular mechanisms of troponin-tropomyosin-related regulation of muscle contraction in a single muscle fiber. It is believed that tropomyosin residue Glu150 is not directly involved in the interaction of tropomyosin with actin and myosin interactions; however, according to structural models of thin filaments under low Ca²⁺ conditions, this residue is located close to site of binding with the C-terminal domain of troponin I. To assess the performance of myosin heads in the presence of Glu150Ala mutant tropomyosin, we measured the polarized fluorescence of 1,5-IAEDANS probe bound to the SH1-helix of myosin. The obtained results indicate an abnormal increase in the number of myosin heads strongly bound to actin during relaxation of muscle fibres containing Glu150Ala mutant tropomyosin. It has been shown that the green tea catechin epigallocatechin gallate (EGCG), known as a modulator of troponin function, inhibits the premature transition of myosin heads into a state of strong actin binding, and thus weakens the damaging effect of the mutation. However, EGCG does not completely restore the effective behavior of myosin cross-bridges during the ATPase cycle.