On mice, rabbits, and human heart failure.

Sarcomeres, bundled into thick and thin filaments, are the units of contraction in the striated muscle. The thick filaments comprise several hundred hexameric myosin molecules, composed of 2 myosin heavy chain (MyHC) proteins, the molecular motor of contraction, and 2 regulatory and 2 essential light chains. The globular head of MyHC contains the binding domains for cardiac -actin and adenosine triphosphate (ATP) and is attached to a hinge region, which when flexed, moves the globular head over the thin filaments. The thin filaments comprise the cardiac troponin C (cTnC), T (cTnT), and I (cTnI) complex, -tropomyosin dimers, and cardiac -actin, maintained in a tight 1:1:7 stoichiometry. Several additional sarcomeric proteins, such as myosin-binding protein C, titin, obscurin, and telethonin contribute to the stabilization and function of the sarcomeres.