Myosin is a family of motor proteins that convert chemical energy from ATP into mechanical work, powering everything from the contraction of your biceps to the transport of tiny cargo inside individual cells. A typical myosin molecule has a head that grips protein filaments called actin, a neck region that acts as a lever, and a tail that connects to whatever the motor needs to pull or carry. While most people associate myosin with muscle, the superfamily extends far beyond that: there are dozens of classes found across plants, fungi, and single-celled organisms, doing jobs that range from cell division to hearing.
How a Myosin Molecule Is Built
Despite the diversity of the superfamily, most myosins share a recognizable architecture built around three regions. The heavy chain forms the backbone of the molecule, starting with a head domain (also called the motor domain) at one end. This head contains two critical pockets: one that binds and breaks down ATP, and another that latches onto actin filaments. Following the head is a neck domain where smaller proteins called light chains wrap around and stiffen the structure, forming what researchers call the lever arm. Finally, a tail domain at the opposite end serves different purposes depending on the myosin class. In muscle myosin, tails coil together with other myosin molecules to form thick filaments. In transport myosins, the tail grabs onto cellular cargo like vesicles or organelles.1PubMed Central. Structural and functional insights on the Myosin superfamily
The heavy chains of different myosin types are more alike in their heads than in their tails, which makes sense: the engine that grips actin and burns fuel is fundamentally similar across classes, while the tail end has evolved to suit whatever job a particular myosin performs. In some classes the tail contains coiled-coil regions that let heavy chains bundle together; in others it carries specialized binding domains that recognize specific membranes or protein partners.2PubMed. Coevolution of head, neck, and tail domains of myosin heavy chains
The Power Stroke
The central trick myosin performs is converting chemical energy into a physical tug. This happens through a repeating cycle sometimes called the cross-bridge cycle, and the key event within it is the power stroke. When ATP binds to the myosin head, it causes the head to release actin and cock its lever arm into a “ready” position. The head then splits ATP into ADP and phosphate, and when it reattaches to actin and releases the phosphate, the lever arm swings forward by roughly 60 degrees, dragging the actin filament along with it. That swing is the power stroke. Afterward, ADP leaves, a fresh ATP arrives, and the cycle starts again.3PubMed Central. Structural mechanism of the recovery stroke in the myosin molecular motor
The timing of phosphate release has been a subject of intense study. Research using phosphate-mimicking molecules has shown that the transition from weak, loosely attached binding to strong, force-generating binding can actually begin before phosphate fully exits the active site. In other words, the head starts gripping tightly and initiating the stroke while the phosphate is still sitting in the pocket, rather than waiting for it to leave first.4PubMed Central. Initiation of the power stroke in muscle: insights from the phosphate analog AlF4
Between power strokes, the lever arm has to reset. This “recovery stroke” involves closing the ATPase site to activate it for the next round of fuel splitting, while simultaneously rotating the lever arm back to its starting position. The two events are linked by a cascade of shape changes along a structure called the relay helix, which acts like a transmission line connecting the fuel-burning site to the force-generating arm.3PubMed Central. Structural mechanism of the recovery stroke in the myosin molecular motor
Muscle Contraction
The most familiar role for myosin is in skeletal and cardiac muscle, where it works as part of the sarcomere, the basic contractile unit. Inside each sarcomere, thick filaments made of bundled myosin II molecules interdigitate with thin filaments made of actin. When a nerve signal triggers calcium release, myosin heads along the thick filament engage with actin and cycle through their power strokes, pulling the thin filaments inward and shortening the sarcomere. Multiply that by billions of sarcomeres in series and in parallel, and you get the contraction of a whole muscle. This sliding-filament model was first proposed in 1954 by Hugh Huxley and Jean Hanson, and it remains the foundational framework for understanding how muscles generate force.5PubMed Central. Hugh E. Huxley: the compleat biophysicist
Not all muscle myosin is created equal. The heart, for instance, expresses two isoforms of the myosin heavy chain known as alpha and beta. Alpha myosin has a much faster ATPase rate and cycles through the power stroke about ten times faster than beta, giving it higher contractility. Hearts that predominantly express alpha myosin contract more vigorously than those dominated by the slower beta form. Interestingly, the motor domains of the two isoforms share about 91% of their amino acid sequence, yet the clusters of differing residues sit in regions that control actin binding, ATP splitting, and force output, which explains how such small sequence differences translate into large functional differences.6PubMed Central. Identification of functional differences between recombinant human α and β cardiac myosin motors7Journal of Molecular Biology. Full-length rat alpha and beta cardiac myosin heavy chain sequences
Smooth muscle, found in blood vessel walls, airways, and the digestive tract, uses a different regulatory strategy. Rather than relying on the troponin system used by skeletal and cardiac muscle, smooth muscle contraction is primarily governed by the phosphorylation of myosin’s regulatory light chains. A calcium-dependent enzyme called myosin light chain kinase adds a phosphate group to the light chain, which activates the myosin head and allows cross-bridge cycling. Relaxation occurs when a phosphatase removes that phosphate.8PubMed. Invited review: regulation of myosin phosphorylation in smooth muscle
Intracellular Transport
Outside of muscle, a different set of myosins carry cargo through the cell’s interior. Myosin V is the best-studied transport motor. Rather than working in large bundles like muscle myosin, a single two-headed myosin V molecule walks along an actin filament in a hand-over-hand fashion, with each head stepping about 74 nanometers forward while the other head stays planted. This gait, confirmed by single-molecule fluorescence experiments, is fundamentally different from an inchworm-like motion where both halves of the molecule would move the same distance. Myosin V carries vesicles, pigment granules, and mRNA to specific destinations inside cells.9Biophysical Journal. Nanometer Localization of Single Green Fluorescent Proteins: Evidence that Myosin V Walks Hand-Over-Hand via Telemark Configuration
Myosin VI is the oddball of the family: it walks in the opposite direction. Most myosins move toward the “plus” end of actin filaments, but myosin VI heads toward the minus end. The reversal traces to a short structural insert at the end of the motor domain that repositions the lever arm. When researchers removed this insert, the motor switched back to plus-end movement. Conversely, leaving it in place was sufficient to maintain minus-end travel. Myosin VI uses this reversed movement to participate in endocytosis, pulling material inward from the cell surface.10PubMed Central. The unique insert at the end of the myosin VI motor is the sole determinant of directionality
Roles Beyond Movement
If you think of myosin as purely a motor that hauls things from point A to point B, you are missing a large part of the picture. Unconventional myosins participate in organizing the actin cytoskeleton itself, regulating the mitotic spindle during cell division, and even influencing gene transcription inside the nucleus.11PubMed Central. Unconventional myosins acting unconventionally
Nonmuscle myosin II, for example, is a workhorse of cell architecture. It generates the contractile forces needed for cell migration, tissue remodeling, and adhesion to surfaces. During cell division, nonmuscle myosin II assembles into a ring at the cell’s equator and squeezes, pinching the dividing cell into two daughters. This contractile ring must assemble, constrict, and disassemble with precise timing; disrupting the process leads to failed division or abnormal cell blebbing.12PubMed Central. Mammalian nonmuscle myosin II comes in three flavors13Journal of Cell Science. Non-muscle myosin 2 at a glance – Section: Cell division
Getting myosin II to the right place during cytokinesis requires a two-step signaling process. Initial recruitment to the equatorial cortex depends on a signaling cascade involving the Rho1 pathway and an enzyme called Rho kinase. Maintaining myosin at the furrow, however, requires a functioning actin network assembled by a separate set of proteins. Without that actin scaffold, myosin II drifts away from the equator and pops up erratically around the cell surface, sometimes triggering abnormal contractions.14PubMed Central. Distinct pathways control recruitment and maintenance of myosin II at the cleavage furrow during cytokinesis
Myosin X is another unconventional family member with a distinctive job. It concentrates at the tips of filopodia, the thin finger-like protrusions cells extend to explore their environment. Myosin X not only localizes to these tips but actively promotes filopodia formation, playing a role in cell migration and the invasive behavior of certain cancer cells.15PubMed Central. Myosin-X: a MyTH-FERM myosin at the tips of filopodia
Myosin in Hearing
Your ability to hear depends on myosin. Inside the inner ear, sensory hair cells detect sound vibrations through tiny projections called stereocilia, which are connected by thread-like structures called tip links. These tip links pull open ion channels when sound waves deflect the stereocilia. Myosin VIIa sits at the upper end of the tip link and helps set its tension, which determines how sensitive the channel is to deflection. In mice carrying mutations that disrupt the tail of myosin VIIa, the resting open probability of the mechanotransduction channel in inner hair cells drops substantially, and the activation curve shifts, meaning more deflection is needed to trigger the same response. These animals effectively become hard of hearing.16Nature Communications. Myosin-VIIa is expressed in multiple isoforms and essential for tensioning the hair cell mechanotransduction complex
In humans, mutations in the gene encoding myosin VIIa cause Usher syndrome type 1B, the most common cause of combined hereditary deafness and blindness. The connection makes sense once you realize the same motor protein is needed to maintain the structural integrity of both stereocilia in the ear and photoreceptor cells in the retina.
When Myosin Goes Wrong
Because myosin is so central to so many processes, mutations in myosin genes lead to a wide range of diseases. Mutations in the MYH7 gene, which encodes the beta cardiac myosin heavy chain, are among the most common genetic causes of hypertrophic cardiomyopathy, a condition in which the heart muscle thickens abnormally. Patients with MYH7 mutations tend to have higher rates of cardiac conduction disease and ventricular arrhythmias compared to patients whose hypertrophic cardiomyopathy stems from mutations in other sarcomeric genes.17PubMed Central. A Family with Myh7 Mutation and Different Forms of Cardiomyopathies
Mutations in MYH9, the gene for nonmuscle myosin IIA’s heavy chain, cause a multi-system disorder. About 30% of people with MYH9-related disease develop nephropathy, which can progress rapidly. The condition also causes blood abnormalities including abnormally large platelets and low platelet counts, along with cataracts and sensorineural hearing loss. The combination of kidney, blood, eye, and ear involvement reflects just how widely nonmuscle myosin IIA is used across different tissues.18PubMed Central. MYH9 nephropathy
Targeting Myosin With Drugs
The understanding of myosin’s mechanism has opened the door to drugs that deliberately manipulate its activity. The most prominent example is mavacamten, a small-molecule inhibitor of cardiac myosin approved for treating obstructive hypertrophic cardiomyopathy. Rather than blocking myosin from ever interacting with actin, mavacamten works on multiple steps of the cross-bridge cycle. Its primary effect is slowing the rate of phosphate release, the step that triggers the power stroke. It also reduces the number of myosin heads that transition from weak binding to the strong, force-generating state.19Journal of Biological Chemistry. Mechanism of Action of the Small-Molecule Cardiac Myosin Inhibitor Mavacamten (MYK-461)
A particularly elegant feature of mavacamten is that it stabilizes an autoinhibited conformation in which the two heads of a myosin molecule fold back against each other, a state called the “super-relaxed state.” In this conformation the heads are effectively parked along the thick filament and unable to engage actin, which simultaneously reduces force generation and lowers the heart’s energy consumption. For a thickened, overworked heart, this calms the excessive contractility that drives symptoms like outflow tract obstruction while also improving energy efficiency.20PubMed Central. Mavacamten stabilizes an autoinhibited state of two-headed cardiac myosin21PubMed Central. Mavacamten Cardiac Myosin Inhibitor: Clinical Applications and Future Perspectives
Myosin in Plants
Animals do not have a monopoly on myosin. Plants rely on their own classes, particularly myosin XI, to drive cytoplasmic streaming, the continuous circulation of cell contents that distributes nutrients, organelles, and signaling molecules. Plant cells can be enormous compared to animal cells, so passive diffusion alone would be far too slow to move materials from one end to the other. Myosin XI solves this by hauling organelles along actin filaments at impressive speeds.22PubMed. Actin-myosin XI: an intracellular control network in plants
How impressive? Single molecules of tobacco myosin XI move processively along actin at about 7 micrometers per second, taking 35-nanometer steps. That makes it the fastest known processive myosin. The trade-off is that it generates relatively low force per step; it is optimized for speed rather than heavy lifting. Watching cytoplasmic streaming under a microscope, you can see organelles whipping around the cell interior at a pace that seems almost frantic, and myosin XI is the engine behind it.23PubMed Central. Higher plant myosin XI moves processively on actin with 35 nm steps at high velocity
How Scientists Measure Single Myosin Molecules
Much of what we know about myosin comes from experiments that manipulate individual molecules. Optical tweezers, which use focused laser beams to trap and exert controlled forces on tiny beads attached to myosin or actin, have been a central tool. In a typical setup, a single actin filament is suspended between two beads held by laser traps, and a surface-mounted myosin head is allowed to interact with it. Researchers can then measure the size and duration of each power stroke with nanometer and piconewton precision. Measurements of rabbit muscle myosin, for example, show single-interaction displacements of about 15 to 20 nanometers and forces near 1.7 to 1.8 piconewtons.24PubMed Central. Single-molecule mechanics of heavy meromyosin and S1 interacting with rabbit or Drosophila actins using optical tweezers
Optical tweezers experiments have also revealed that some myosins produce their power stroke in distinct phases. Myosin-10, the filopodia specialist, generates an initial 15-nanometer displacement followed by a smaller 2-nanometer shift under moderate load. At very low loads, it walks processively along a single actin filament in staircase-like steps of about 35 nanometers, taking as many as six consecutive steps before letting go.25PubMed Central. Myosin-10 produces its power-stroke in two phases and moves processively along a single actin filament under low load
Evolutionary Depth of the Myosin Superfamily
Myosin is ancient. The last common ancestor of all eukaryotes likely had at least two myosins: a class I prototype and a second myosin that gave rise to every other class. From that starting point, the family expanded dramatically, with new classes and new tail-domain architectures appearing at key moments in evolutionary history.26PubMed Central. Myosin repertoire expansion coincides with eukaryotic diversification in the Mesoproterozoic era
A major burst of myosin diversification occurred at the base of the animal lineage and its close relatives, predating the origin of multicellularity. This expansion may have helped provide the cellular machinery needed for the more complex tissue organization and cell-cell communication that multicellular life demands.27PubMed Central. Evolution and Classification of Myosins, a Paneukaryotic Whole-Genome Approach
Genome-wide surveys have identified over 35 myosin classes so far, spread across organisms as different as humans, fruit flies, parasitic protists, and diatom algae. Some of these classes carry tail domains that have never been seen on other myosins, suggesting that the superfamily has repeatedly co-opted new protein modules to take on new cellular jobs. The diversity is so broad that the classification system has been revised multiple times as genomic data from more species become available.28PubMed Central. New insights into myosin evolution and classification