The interactions between motor proteins bring changes in cells

In this article, I briefly describe how the interactions of motor proteins bring changes in cells.

Table of Contents

The activity of motor proteins

The movement of organelles and macromolecules within cells mainly arises from the activity of molecular motors. Motor proteins in large aggregates gaining energy from ATP undergo cyclic conformational changes that concentrate into a unified directional tiny force that pulls apart chromosomes in a dividing cell. The interactions among motor proteins get high levels of spatial and temporal organization.

The movement of proteins, kinesins, and dyneins along cell microtubules results in the pulling of cell organelles and reorganizing chromosomes during cell division. The protein dynein interacts with microtubules and gives motion to eukaryotic cilia and flagella. The proteins, like helicases and polymerases along with some other proteins, carry out their functions in DNA metabolism while moving along DNA.

Actin and Myosin- The two important muscle proteins

The two major muscle proteins, actin and myosin are arranged in filaments, which bring the contractile force to the muscle. These two proteins undergo transient interactions and slide past each other to bring the contraction in muscle. Above 80% of muscle mass is composed of actin and myosin.

Actin

The muscle protein, actin is found to abound in almost all eukaryotic cells. The molecules of monomeric actin, also called G-actin (globular actin), get associated to form a long polymer known as F-actin (filamentous actin) in muscle.

The two proteins, troponin, and tropomyosin, along with the F-actin, constitute the thin filament, where the filamentous parts assemble as successive monomeric actin molecules at one end.

As each monomer binds ATP, so each actin molecule in the filament is complex to ADP. In the thin filament, each actin monomer can bind specifically and tightly to one myosin head group.

Myosin

Myosin consists of four light chains and two heavy chains. The heavy chains occupy most of the structure of the protein. The heavy chains at their carboxyl termini wrapped around each other in a left-handed coiled coil like the protein alpha-keratin. The hydrolysis of ATP takes place at a large globular domain in each heavy chain at its amino-terminal end.

The globular domains have an association with the light chains too. The protease trypsin cleaves much of the fibrous tail of myosin and divides the protein into light and heavy meromyosin.

The globular domain of myosin called S1, which is the myosin head group, is free from heavy meromyosin by cleavage with the enzyme papain, which leaves myosin sub-fragment S2. Contraction in muscles is possible by the motor domain S1 fragment of myosin.

In muscle cells, the core of the contractile unit are the rod-like structures known as thick filaments. These filaments are formed by the aggregation of molecules of myosin. Many myosin molecules within a filament are arranged with their fibrous tail associated, forming a long bipolar structure.

The thick and thin filaments are made into ordered structures by additional proteins

Structure of a muscle fiber

A muscle fiber is a very large, single multinucleated cell with a diameter ranging from 20 to 100µm in diameter. Skeletal muscle consists of parallel bundles of muscle fibers and a single muscle fiber, generally extending over the length of the muscle.

Each muscle fiber consists of about a thousand myofibrils. Each myofibril having a diameter of 2µm consists of a huge number of regularly arrayed thick and thin filaments, complex to other proteins. Flat membranous vesicles surround each myofibril called the sarcoplasmic reticulum.

A muscle fiber under an electron microscope

A muscle fiber under an electron microscope shows alternating regions of high and low electron density known as A bands and I bands. The A bands and I bands arise from the arrangement of thick and thin filaments, respectively.

The darker A band includes the region where parallel thick and thin filaments overlap. The presence of a thin structure called the Z disk, which is perpendicular to the thin filaments. The Z disc also acts as an anchor to which the thin filaments are attached.

The Z disc is produced by bisecting the I band, whereas the A band is bisected by a thin line, the M line, or the M disc. The M line is a high electron density region in the middle of the thick filaments.

The bundles of thick filaments are interweaved at either end with bundles of thin filaments. This constitutes the whole contractile unit known as the sarcomere. These interweaved arrangements of bundles of thick and thin filaments allow them to slide past each other, ultimately causing the progressive shortening of each sarcomere.

More muscle proteins

At one end of the Z disk, there is the attachment of thin actin filaments. The thin actin filaments consist of minor muscle proteins, α-actinin, desmin, and vimentin, and a large protein called nebulin. The M line is attached with thick filaments consisting of proteins like para myosin, C-protein, and M-protein.

The thick filaments are linked to the Z disc by another group of proteins called titins (the largest single polypeptide chains) to give additional organization to the overall structure. The length of the thin and thick filaments is regulated by the proteins nebulin and titin, respectively.

The length of the sarcomere is regulated by the protein titin, extending from the Z disc to the M line. Thus, the overextension of the muscle is also regulated.

The interaction between actin and myosin

The interaction between actin and myosin involves a weak bond type. When myosin is bound to ATP, it is hydrolyzed to ADP and phosphate. This results in a coordinated and cyclic series of conformational changes in myosin. Due to this, myosin releases the F-actin subunit and binds another subunit farther along the actin filament. However, when myosin is not bound to ATP, a face on the myosin head group binds tightly to actin.

The molecular mechanism of muscle contraction

The molecular mechanism of muscle contraction initiates with the binding of ATP to myosin. The binding opens a cleft in myosin, disrupting the actin-myosin binding and the release of the bound actin.

In the second step, ATP is hydrolyzed to ADP and phosphate. The hydrolysis of ATP causes a conformational change in myosin to a high-energy state. This changes the orientation of the myosin head. After detachment from actin, myosin weakly binds to an F-actin subunit closer to the Z disc.

In the third step, the phosphate is released from myosin. This results in another conformational change in myosin, leading to the closure of the myosin cleft. Thus, it strengthens the myosin-actin binding.

The third step is quickly followed by the fourth step, which pertains to the change in conformation of myosin head and returning to the original resting state. Then, ADP is released to complete the cycle.

In a thick filament there is presence of many myosin heads and some are bound to thin filaments. When an individual myosin head releases the bound actin subunit, the myosin heads prevent thick filaments from slipping backward. Thus, the thick filament promptly slides forward past the adjacent thin filaments. This process is harmonized among many sarcomeres in muscle fiber and ultimately brings muscle contraction.

The working of two proteins tropomyosin and troponin

Muscle contraction occurs only when getting any signals from the nervous system. It also depends upon the regulation of interaction between actin and myosin. The regulation is brought about by two proteins, tropomyosin and troponin.

Tropomyosin blocks the attachment sites for the myosin head groups by binding to the thin filament. The sarcoplasmic reticulum releases Ca²⁺ ions because of a nerve impulse. Troponin is a Ca²⁺ binding protein, which binds to the released Ca²⁺ ions. This binding causes a conformational change in the tropomyosin-troponin complexes by exposing the myosin-binding sites on the thin filaments. This step is followed by muscle contraction.

The interaction between actin and myosin is similar to that of protein and ligand-like interaction between immunoglobulin and antigen. The interaction is reversible and leaves the participant unchanged. Myosin is not only an actin-binding protein but an ATPase, an enzyme. The binding of ATP to myosin hydrolyzes ATP to ADP and inorganic phosphate (Pi).

Conclusion

The interactions among motor proteins bring changes in cells. The activity of molecular motors initiates the movement of organelles and macromolecules within cells. The contractile force in the muscle is due to the presence of two major muscle proteins, actin, and myosin.

The binding of ATP to myosin initiates the molecular mechanism of muscle contraction. Muscle contraction occurs after getting any signals from the nervous system. It also depends upon the regulation of interaction between actin and myosin. The two regulatory proteins, tropomyosin and troponin regulate the interaction between actin and myosin.