WangCompPhysiol'18.pdf

Sarcomeres consist of highly ordered arrays of thick myosin and thin actin filaments along with
accessory proteins. Thick filaments occupy the center of sarcomeres where they partially overlap
with thin filaments. The sliding of thick filaments past thin filaments is a highly regulated process
that occurs in an ATP-dependent manner driving muscle contraction. In addition to myosin that
makes up the backbone of the thick filament, four other proteins which are intimately bound to the
thick filament, myosin binding protein-C, titin, myomesin, and obscurin play important structural
and regulatory roles. Consistent with this, mutations in the respective genes have been associated
with idiopathic and congenital forms of skeletal and cardiac myopathies. In this review, we aim to
summarize our current knowledge on the molecular structure, subcellular localization, interacting
partners, function, modulation via posttranslational modifications, and disease involvement of
these five major proteins that comprise the thick filament of striated muscle cells.