Subcell Biochem. 2026;113:35-58. doi: 10.1007/978-3-032-05273-5_2.
ABSTRACT
Striated muscle is composed of overlapping arrays of thick myosin filaments and thin actin filaments. The thick filaments are composed of myosin molecules, which are hexamers of two heavy chains and two pairs of light chains. The heavy chain has an N-terminal head domain and a C-terminal helical rod domain. The latter dimerises to form a two-stranded coiled-coil rod. The distal two-thirds of these rods aggregate in parallel to form the filament backbone, while the heads lie on the surface to facilitate interactions with actin. The molecules aggregate in an antiparallel manner in the centre of the A-band to form the so-called bare zone. The proximal one-third of the rod can swivel and thereby allow the myosin heads to interact with actin. The atomic structure of the head, determined in the 1990s, was a major milestone in the muscle field. Over the next three decades, great strides were made in cryo-electron microscope technology and software. This led to the high-resolution structure of the insect flight muscle thick filament, showing the structure of the myosin tails at 6 Å resolution and the structure of the heads. There has been great excitement recently with the high-resolution structures of relaxed cardiac muscle thick filaments showing details of all the important players: three types of myosin crowns and the paths of their tails, the structure and interactions of cMyBP-C and the structure of two unique forms of titin and its role in filament assembly. Hypertrophic cardiomyopathy, which results from mutations in sarcomeric proteins, especially myosin and cMyBP-C, is a major health burden and insight gained from the new studies will help to devise new therapies.
PMID:41557228 | DOI:10.1007/978-3-032-05273-5_2