Myosin: structure, synthesis, classification, function

Skeletal muscle contraction is fundamental to all animal movements, from simple locomotion to complex manipulations. This contraction is carried out by contractile proteins within muscle cells, particularly actin and myosin, which form myofibrils. Myofibrils are further divided into sarcomeres, the functional units of muscle contraction. Actin forms the thin filaments, whereas myosin constitutes the thick filaments and plays a key role in the sliding filament model of muscle contraction. Myosin is not restricted to muscle tissue and also contributes to various cellular functions in non-muscle cells, such as cell adhesion and migration.

This article describes the structure, synthesis, classification, and diverse roles of myosins, focusing on their essential functions in muscle contraction and cellular processes.

Myosin structure

Myosin is a fibrous protein classified as a motor protein due to its ability to convert chemical energy from ATP hydrolysis into mechanical work. A single myosin molecule is composed of six subunits: two heavy chains and four light chains. The structural organization of these chains is essential for myosin function.

• Heavy chainThe two heavy chains wrap around each other to form a double helix, which makes up the tail of the myosin molecule. This tail forms the bulk of myosin’s structure.
• Myosin HeadAt one end of the heavy chain, myosin branches to form a globular structure called a myosin head or crossbridge. Each head contains an ATPase site and an actin-binding site.
• Light chainEach globular head is associated with two light chains, which stabilize the head structure.

Overall, the myosin molecule consists of two heads and one tail, forming a unique structure necessary for its function.

Myosin domains

To understand the function of myosin, it is helpful to consider three major domains:

1. Head DomainThis domain is globular and consists of a heavy chain end and two light chains. It is responsible for binding to actin filaments and has the ATPase activity essential for muscle contraction.
2. Neck areaThe neck domain acts as a linker between the head and the tail and is essential for transmitting the force generated by the head to the tail. It also connects the light chains.
3. Tail DomainThe tail domain formed by the coiled-coil structure of the heavy chain connects myosin molecules within the filament and interacts with cargo molecules in nonmuscle cells.

Myosin synthesis

Myosin synthesis is a complex process involving multiple steps of gene expression.

Transcription

The process begins with transcription, where the DNA sequence of a myosin gene is copied into messenger RNA (mRNA). This occurs in the nuclei of muscle and non-muscle cells. Each gene corresponds to a specific myosin isoform, and only one gene is transcribed at a time.

Post-transcriptional modifications

To prepare the mRNA for translation, several modifications are made.

• 5ft Cap: A guanosine triphosphate (GTP) cap is added to the 5′ end of mRNA to protect it from degradation and help initiate translation.
• PolyA tail: A polyadenylation tail is added to the 3′ end, further protecting the mRNA and facilitating export to the cytoplasm.

translation

Once in the cytoplasm, the mRNA is translated into myosin protein. Ribosomes assemble around the mRNA, and transfer RNA (tRNA) molecules deliver amino acids to the ribosome according to the mRNA sequence. This process continues until a stop codon is reached, signaling the end of translation. The newly synthesized myosin protein then undergoes post-translational modifications in the endoplasmic reticulum.

Post-translational modifications

Post-translational modifications are important for the functional maturation of myosin.

• PhosphorylationThe addition of a phosphate group to serine, threonine, or tyrosine residues, catalyzed by myosin light chain kinase, activates or inactivates the function of myosin.
• Nitration and Nitrosylation: Under pathological conditions, addition of nitrate or nitro groups can occur, affecting myosin function and causing contractile dysfunction.

Types of myosin

Myosins are classified into several types based on their structure, location, and function. The main classes are:

1. Myosin IMonomeric protein involved in intracellular trafficking and membrane interactions.
2. Myosin II: Classical muscle myosin responsible for muscle contraction. Found in skeletal, smooth, and cardiac muscles.
3. Myosin IIIIt is present in the Drosophila eye and is involved in light-dependent transduction.
4. Myosin VDimeric protein that “walks” along actin filaments; essential for intracellular transport.
5. Myosin VI: Plays a role in transporting endocytic vesicles within the cell.
6. Myosin VII: Involved in phagocytosis and spermatogenesis, present in some sensory structures.
7. Myosin VIIIIt is present in plant cells and regulates cell division and cytoplasmic flow.
8. Myosin XIA dimeric protein involved in organelle movement within plant cells.

Myosin plays a central role in muscle contraction through its interaction with actin filaments, the mechanism by which it does so differs slightly between skeletal, smooth, and cardiac muscles.

Skeletal muscle

In skeletal muscle, myosin filaments are located at the center of the sarcomere, with actin filaments extending from both ends. Myosin heads bind to actin filaments when binding sites are exposed by calcium ion release. ATP hydrolysis promotes a conformational change in the myosin head, resulting in a power stroke that pulls the actin filament toward the center of the sarcomere. This sliding mechanism of the filaments results in muscle contraction.

Smooth muscle

Smooth muscle contraction is controlled differently. Myosin filaments are intermingled with actin filaments attached to the compact body. Unlike skeletal muscle, smooth muscle lacks troponin and tropomyosin. Instead, contraction is controlled by phosphorylation of myosin light chains by myosin light chain kinase, which is activated by calcium ions. This process causes myosin heads to bind to actin, driving contraction.

Myocardium

Cardiac muscle contraction occurs via a similar mechanism to skeletal muscle, where myosin filaments are arranged into sarcomeres, again following the sliding filament model, and calcium ions trigger the contractile process.

summary

Myosin is an important protein in muscle contraction and various cellular processes. Its structure, consisting of two heavy chains and four light chains, is essential for its function. Myosin synthesis involves transcription, translation, and post-translational modifications. Based on their function and location, myosins are classified into different types, including muscle and non-muscle.

During muscle contraction, myosin interacts with actin filaments through a sliding filament mechanism. Although the fundamental process is similar across muscle types, the regulatory mechanisms differ between skeletal, smooth, and cardiac muscles. Understanding myosin structure and function provides insight into the diverse roles of myosin in both muscle physiology and cellular processes.

Actin: Structure, Function, and Dynamics – Science Notes