Myosin belongs to the motor proteins and is responsible, among other things, for the processes involved in muscle contraction. There are several types of myosins, all of which participate in transport processes of cell organelles or in displacements within the cytoskeleton. Structural abnormalities in the molecular structure of myosin can be causes of muscle diseases in some circumstances.
What is myosin?
Myosin, along with dynein and kinesin, is one of the motor proteins responsible for the processes of cell movement and transport within the cell. Unlike the other two motor proteins, myosin functions only in conjunction with actin. Actin, in turn, is a component of the cytoskeleton of the eukaryotic cell. Thus, it is responsible for the structure and stability of the cell. Furthermore, actin, together with myosin and two other structural proteins, forms the actual contractile structural unit of the muscle. Two-thirds of the muscle’s contractile proteins are myosins and one-third is actin. However, myosins are present not only in muscle cells but also in all other eukaryotic cells. This is true for unicellular eukaryotes as well as for plant and animal cells. The microfilaments (actin filaments) are involved in the assembly of the cytoskeleton in all cells and, together with myosin, control protoplasmic currents.
Anatomy and structure
Myosins can be divided into several classes and subclasses. Currently, over 18 different classes are known, with classes I, II, and V being the most significant. The myosin found in muscle fiber is called conventional myosin and belongs to class II. The structure of all myosins is similar. They all consist of a head part (myosin head), a neck part and a tail part. Here, the myosin filaments of skeletal muscle consist of approximately 200 myosin II molecules, each with a molecular weight of 500 kDa. The head part is genetically very conservative. The classification into structural classes is mainly determined by the genetic variability of the tail part. The head part binds to the actin molecule, while the neck part acts as a hinge. The tail portions of several myosin molecules cluster together to form filaments (bundles). The myosin II molecule consists of two heavy chains and four light chains. The two heavy chains form a so-called dimer. The longer of the two chains has an alpha-helix structure and is composed of 1300 amino acids. The shorter chain consists of 800 amino acids and represents the so-called motor domain. It forms the head part of the molecule, which is responsible for the movements and transport processes. The four light chains are connected to the head and neck part of the heavy chains. The light chains farther from the head are called regulatory chains and the light chains near the head are called essential chains. They have a high affinity for calcium and thus can control the mobility of the neck part.
Function and roles
The most important function of all myosins is to transport cell organelles and perform displacements within the cytoskeleton in eukaryotic cells. In this process, the conventional myosin II molecules, together with actin and the proteins tropomyosin and troponin, are responsible for muscle contraction. To this end, myosin is first integrated into the Z-disks of the sacomere with the help of the protein titin. Six titin filaments fix a myosin filament for this purpose. In the sacomer, a myosin filament forms about 100 cross connections to the sides. Depending on the structure of the myosin molecules and the content of myoglobin, several forms of muscle fibers can be distinguished. Within the sacomer, muscle contraction takes place through the movement of myosin in the cross-bridge cycle. First, the myosin head is tightly attached to the actin molecule. Then ATP is cleaved to ADP, and the energy released leads to the tension of the myosin head. At the same time, the light chains provide an increase in calcium ions. This causes the myosin head to attach to an adjacent actin molecule as a result of a conformational change. With the old bond released, the tension is now converted into mechanical energy by what is called a force stroke. The movement is similar to an oar stroke. In the process, the myosin head tilts from 90 degrees to between 40 and 50 degrees. The result is a muscle movement.During muscle contraction, only the length of the sacomer is shortened, while the lengths of actin and myosin filaments remain the same. The ATP supply in the muscle only lasts for about three seconds. By breaking down glucose and fat, ATP is made again from ADP, so that chemical energy can continue to be converted into mechanical energy.
Diseases
Structural changes in myosin caused by mutations can lead to muscle diseases. One example of such a disease is familial hypertrophic cardiomyopathy. Familial hypertrophic cardiomyopathy is an inherited disease that is inherited in an autosomal dominant manner. The disease is characterized by thickening of the left ventricle of the heart without dilatation. It is a relatively common heart disease with 0.2 percent prevalence in the general population. This disease is caused by mutations that lead to structural changes in betamyosin and alphatropomyosin. This involves not one, but multiple point mutations of the proteins involved in the construction of the sacomer. Most of the mutations are located on chromosome 14. Pathologically, the disease manifests itself by a thickening of the muscles in the left ventricle. This asymmetry in myocardial thickness can result in cardiovascular symptoms including arrhythmias, dyspnea, dizziness, loss of consciousness, and angina pectoris. Although many patients have little or no impairment of cardiac function, progressive heart failure may develop in some circumstances.