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Molecular mechanism of Ca-dependent regulation of cardiac muscle contraction in health and disease
Striated muscle contraction
is regulated by Ca2+, which binds to the troponin (Tn) complex located on the
thin filament. Ca2+-binding to TnC, one of the Tn components, triggers a series
of structural change among the thin filament proteins, subsequently allowing
the interaction of the thick and thin filaments. The regulation by Ca2+-activation
of cardiac muscle is fine-tuned by covalent modification, such as phosphorylation
of the myofilament proteins, including TnI and TnT. Using biochemical, biophysical
and molecular biology methods, we are investigating how the Ca2+-binding to
TnC activates the thin filament to initiate contraction and how this event is
modified by covalent modification under the pathophysiological conditions.