Myosin is a fundamental motor protein found in nearly all eukaryotic cells, acting as the cell’s internal engine for movement and force generation. This protein’s primary function involves converting the chemical energy stored in adenosine triphosphate (ATP) into mechanical work. Myosin accomplishes this feat by interacting directly with the structural filaments of the cell, primarily actin, to drive processes ranging from muscle contraction to cell division. This molecular machinery is a universal component of biological motion across diverse life forms.
The Molecular Architecture of Myosin
The myosin molecule possesses a distinct structure composed of three functional domains: the head, the neck, and the tail. The globular head domain, also known as the motor domain, is the site of action where both the binding to actin and the hydrolysis of ATP occur. This domain is responsible for the protein’s ability to “walk” along the actin filament, making it the catalytic core of the motor.
The neck region acts as a stiff lever arm, translating the minute conformational changes of the motor domain into larger mechanical displacements. Two types of smaller protein subunits, the essential light chains and the regulatory light chains, bind to this neck region. These light chains stabilize the structure and modulate movement, amplifying the force generated by the motor head.
The tail domain determines the function and cellular location of the specific myosin type. In muscle cells, the tails of multiple myosin molecules aggregate in a coiled-coil structure to form the thick filaments. This aggregation is essential for building the organized structures required for coordinated muscle contraction. The heavy chains constitute the head and tail, while the light chains associate with the neck, completing the functional motor unit.
Powering Muscle Contraction
The most recognized function of myosin, specifically Myosin II, is its role in muscle contraction, explained by the sliding filament model. Within muscle fibers, Myosin II molecules form thick filaments that interdigitate with thin filaments made of actin. Muscle shortening occurs because the thick and thin filaments slide past one another, not because the filaments themselves shrink.
This sliding action is driven by the cyclical interaction between the myosin heads and the actin filaments, known as the cross-bridge cycle. The cycle begins with the myosin head tightly bound to actin (the rigor state). Binding of a new ATP molecule causes the myosin to immediately detach from the actin filament. This detachment is followed by the hydrolysis of ATP into ADP and inorganic phosphate (\(\text{P}_{\text{i}}\)), which “cocks” the myosin head into a high-energy position.
The cocked myosin head then weakly reattaches to a new binding site further along the actin filament, forming a new cross-bridge. The release of the inorganic phosphate (\(\text{P}_{\text{i}}\)) triggers a conformational change in the myosin head, known as the power stroke. This action forces the attached actin filament to slide toward the center of the sarcomere, generating mechanical force and shortening the muscle.
Following the power stroke, the ADP molecule is released from the myosin head, returning the myosin to the strongly bound rigor state. A new ATP molecule can then initiate the next cycle. Multiple myosin heads operate asynchronously, ensuring that a constant pulling force is maintained during contraction.
Myosin’s Diverse Roles Beyond Muscle
While Myosin II is primarily associated with muscle tissue, the myosin superfamily includes over 35 distinct classes performing specialized functions in non-muscle cells. These “unconventional myosins” are generally monomeric or dimeric and do not form the stable filaments characteristic of muscle. They are adapted for single-molecule tasks within the cell’s interior.
Myosin I is a small, single-headed motor often involved in connecting the actin cytoskeleton to the cell membrane, influencing cell shape and membrane dynamics. Myosin V functions as a processive motor, meaning it can take many “steps” along an actin filament without detaching. This efficiency makes it responsible for long-distance transport of cellular cargo, such as vesicles and organelles.
Myosin VI is unusual because it is the only known myosin that moves toward the pointed end of the actin filament, the opposite direction of most others. This unique directionality allows Myosin VI to play a role in endocytosis, where the cell membrane folds inward to bring substances into the cell. Myosin II is also essential in non-muscle cells for cytokinesis, forming the contractile ring that pinches the cell membrane during cell division.
Myosin Dysfunction and Human Disease
Because myosin is central to force generation, mutations in myosin genes are directly implicated in serious human pathologies. The \(\beta\)-cardiac myosin heavy chain (MYH7) gene is a frequent site of mutation leading to two major forms of inherited heart disease. Hypertrophic Cardiomyopathy (HCM) is often caused by mutations that make the myosin heads hyperactive, leading to excessive contractility and thickening of the heart muscle walls.
Conversely, mutations in the same MYH7 gene can result in Dilated Cardiomyopathy (DCM), characterized by a weakened heart muscle and an enlarged ventricular chamber. These mutations reduce the myosin motor’s power output, decreasing the heart’s ability to pump blood effectively. HCM is the most common inherited heart disorder, affecting approximately one in 500 individuals worldwide.
Unconventional myosins also cause disease when mutated, particularly sensory disorders. Defects in Myosin VIIA are the primary cause of Usher syndrome type 1B, resulting in profound congenital deafness and progressive vision loss. This myosin maintains the structure and function of the stereocilia, the tiny actin-based bundles in the inner ear hair cells that convert sound waves into electrical signals.
Similarly, mutations in Myosin VI have been linked to specific forms of hereditary deafness.