The protein tropomyosin is found primarily in striated muscle and participates in muscle contraction. Genetic mutations can affect the structure of the tropomyosin molecules produced, causing a number of diseases-including various forms of cardiomyopathy as well as arthrogryposis multiplex congenita and nemaline myopathy.
What is tropomyosin?
Tropomyosin is a protein found in the human body primarily in skeletal muscle. Biochemist Kenneth Bailey first described the protein in 1946. A single muscle is composed of many muscle fiber bundles, which in turn are composed of the muscle fibers. Each fiber is not composed of a single, clearly delineated muscle cell, but of a tissue with many cell nuclei. Within these units, myofibrils represent finer fibers; their cross-sections are called sarcomeres. A sarcomere consists of two types of strands that are alternately interlocked, as in a gear or zipper. Some of these strands are myosin, and the others are a complex of actin and tropomyosin. In this complex, actin molecules form a thicker chain around which two strands of tropomyosin wind.
Anatomy and structure
Tropomyosin is composed of two parts: α and β. The two building blocks have a total of 568 amino acids, of which 284 are α-tropomyosin and 284 are β-tropomyosin. These amino acids each line up to form long chains, eventually joining together to form a rod-shaped macromolecule. The sequence of amino acids and the structure of the protein are genetically determined; in humans, the following genes are responsible for this: TPM1 on the 15th chromosome, TPM2 on the 9th chromosome, TPM3 on the first chromosome, and TMP4 on the 19th chromosome. The strand of tropomyosin (with both subunits) winds around the thicker actin filaments in striated skeletal muscle. Also attached to it is troponin, another protein.
Function and roles
Tropomyosin is required for the contraction of skeletal muscle. When a nerve impulse reaches the muscle, the electrical stimulus first propagates through the sarcolemma and T-tubules, eventually leading to the release of calcium ions in the sarcoplasmic reticulum. The ions bind transiently to troponin, which is located on the tropomyosin strand. As a result, the calcium ions alter the physical properties of the molecule. The troponin shifts slightly on the surface and thus moves away from the sites where myosin can also bind. Myosin forms the complementary fibers to the actin/tropomyosin complex. At the end of the myosin filament are two so-called heads. The myosin heads can bind to the sites of the actin filament that are now no longer occupied by troponin. After docking to the fiber, the myosin heads flip over, thereby pushing themselves between the actin/tropomyosin filaments, which shortens the sarcomere. At the same time, this process occurs not only in one sarcomere, but in many. The numerous contracted sarcomeres therefore cause the muscle fiber, and thus the muscle as a whole, to contract. In this process, one nerve signal often irritates several hundred muscle fibers. The softening effect of adenosine triphosphate (ATP) allows the myosin head to detach from the actin again. The contraction of smooth muscle is somewhat different. In humans, smooth muscle surrounds organs or occurs in the walls of blood vessels. It can contract more strongly than striated muscle. While skeletal muscle has a striated structure, smooth muscle forms a flat surface consisting of individual cells. In addition to actin and tropomyosin, smooth muscle has two other proteins, caldesmon and calmodulin, whose interaction influences muscle tension. Tropomyosin acts primarily on calmodulin. In addition, tropomyosin also plays a role in other biological processes. For example, it appears to influence the binding of actin in the cytoskeleton and to have an effect on cell division.
Diseases
One disease that may be associated with tropomyosin is hypertrophic cardiomyopathy. This is a heart disease in which the sarcomeres (sections in the muscle fibers) are thickened, which also affects the overall thickness of the muscle fibers.As a result, symptoms such as a feeling of pressure in the chest, dizziness, shortness of breath, syncope and angina pectoris attacks may develop. In this case, they are due to functional problems of the heart muscle. The most common cause (40-60%) of hypertrophic cardiomyopathy is in the genes: Alterations (mutations) lead to errors in the genetic code and, accordingly, to the defective synthesis of proteins. This can also affect the various proteins that make up muscle fibers. In restrictive cardiomyopathy, there is a hardening of the heart muscle. The cause is an excess of connective tissue. Restrictive cardiomyopathy leads to heart failure, which is typically characterized by breathing problems, edema, dry cough, fatigue, exhaustion, dizziness, syncope, palpitations and various digestive problems. Less commonly, affected individuals are confused, suffer from memory problems or limitations in cognitive performance. Dilated cardiomyopathy may also result from a defect in the tropomyosin genes. If this heart disease manifests, it is often accompanied by global heart failure and/or progressive left heart failure. In addition, respiratory disorders, emboli, and cardiac arrhythmias may become apparent. Two other disorders that may be related to tropomyosin, some of which are based on mutations, are nemalin myopathy, in which the muscles may be affected in a variety of ways, and arthrogryposis multiplex congenita, in which the joints stiffen. However, all of these disorders may be due to other causes; mutations at the tropomyosin genes represent only one possibility.
