Actin and myosin

Contraction of muscle follows an increase of Ca " in the muscle cell as a result of nerve stimulation. This initiates processes which cause the proteins myosin and actin to be drawn together making the cell shorter and thicker. The return of the Ca " to its storage site, the sarcoplasmic reticulum, by an active pump mechanism allows the contracted muscle to relax (27). Calcium ion, also a factor in the release of acetylcholine on stimulation of nerve cells, influences the permeabiUty of cell membranes activates enzymes, such as adenosine triphosphatase (ATPase), Hpase, and some proteolytic enzymes and facihtates intestinal absorption of vitamin B 2 [68-19-9] (28). 

Muscle fibers contain myosin and actin which slide against each other during muscle contraction... 

In addition to the major proteins of striated muscle (myosin, actin, tropomyosin, and the troponins), numerous other proteins play important roles in the maintenance of muscle structure and the regulation of muscle contraction. Myosin and actin together account for 65% of the total muscle protein, and tropomyosin and the troponins each contribute an additional 5% (Table 17.1). The other regulatory and structural proteins thus comprise approximately 25% of the myofibrillar protein. The regulatory proteins can be classified as either myosin-associated proteins or actin-associated proteins. 

The molecular events of contraction are powered by the ATPase activity of myosin. Much of our present understanding of this reaction and its dependence on actin can be traced to several key discoveries by Albert Szent-Gyorgyi at the University of Szeged in Hungary in the early 1940s. Szent-Gyorgyi showed that solution viscosity is dramatically increased when solutions of myosin and actin are mixed. Increased viscosity is a manifestation of the formation of an actomyosin complex. 

Inside the typical smooth muscle cell, the cytoplasmic filaments course around the nuclei filling most of the cytoplasm between the nuclei and the plasma membrane. There are two filamentous systems in the smooth muscle cell which run lengthwise through the cell. The first is the more intensively studied actin-myosin sliding filament system. This is the system to which a consensus of investigators attribute most of the active mechanical properties of smooth muscle. It will be discussed in detail below. The second system is the intermediate filament system which to an unknown degree runs in parallel to the actin-myosin system and whose functional role has not yet been completely agreed upon. The intermediate filaments are so named because their diameters are intermediate between those of myosin and actin. These very stable filaments are functionally associated with various protein cytoarchitectural structures, microtubular systems, and desmosomes. Various proteins may participate in the formation of intermediate filaments, e.g., vimentin. 

In order to exert a force from one end of a muscle to the other, a structure must be continuous from one end to the other. In smooth muscle tissue, this structure is a system of alternating myosin and actin filaments within a cell, firm attachments first to the cell membrane, and beyond that extracellular attachments to the... 

Of the several kinase activities which are important in smooth muscle, myosin light chain kinase, MLCK, is the one responsible for activation of the actin-myosin system to in vivo levels. MLCK is present in the other nonmuscle cell types which have the actin-myosin contractile system and all of these are probably activated in a manner similar to smooth muscle rather than by way of the Ca -troponin mechanism of striated muscle. MLCK from smooth muscle is about 130 kDa and is rather variable in shape. It is present in smooth muscle in 1-4 pM concentrations and binds with an equally high affinity to both myosin and actin. Thus, most MLCK molecules are bound to actin. Myosin light chain serine-19 is the primary target of smooth muscle myosin light chain kinase. 

Figure 13.6 Myosin and actin molecules and myosin crossbridges. Each kind of filament is composed of a different protein myosin in the thick filaments and actin in the thin filaments. In the case of actin, the individual F-actins are more or less spherical but a large number of these combine to produce a long chain, two of which wind around each other, rather like a rope, to produce the thin filament. The myosin molecule is more complex and shaped somewhat like a golf club. To form the thick filament, the shafts aggregate to leave the heads protruding on all sides. These heads form the cross-bridges and are responsible for pulling the thin filaments into the spaces between the thick filaments (see Figure 13.5).

In contrast to milk, where samples are primarily derived from cows, meat analysis has to be performed in samples of a widely different animal origin including cattle, lamb, swine, poultry, and fish. Muscle is a complex matrix with a pH of 5.7, composed of muscle fibers, various types of connective tissue, adipose tissue, cartilage, and bones. Sarcoplasmic proteins such as myoglobin, and glycolytic enzymes are soluble in water while the myofibrillar proteins such as myosin and actin are soluble in concentrated salt solutions (14). The connective tissue proteins, collagen and elastin, are insoluble in both solvents. 

The lowered concentrations of calcium ions (Ca++) set off a cascade of cellular reactions that cause the cell s contractile filaments (myosin and actin) to slide apart. 5. Smooth muscle cells relax. 

The contractile force of muscle is generated by the interaction of two proteins, myosin and actin. These proteins are arranged in filaments that undergo transient interactions and slide past each other to bring about contraction. Together, actin and myosin make up more than 80% of the protein mass of muscle. 

Protein-ligand interactions achieve a special degree of spatial and temporal organization in motor proteins. Muscle contraction results from choreographed interactions between myosin and actin, coupled to the hydrolysis of ATP by myosin. 

In the contractile system of skeletal muscle cells, myosin and actin are specialized to transduce the chemical energy of ATP into motion (see Fig. 5-33). ATP binds tightly but noncovalently to one conformation of myosin, holding the protein in that conformation. When myosin catalyzes the hydrolysis of its bound ATP, the ADP and Pi dissociate from the protein, allowing it to... 

In muscle the proteins myosin and actin (Chapter 20) hold most of the ADP leaving only about 0.02 mM free.62 72 The same conclusion has been reached on the basis of other evidence.55... 

Heat and work can be distinguished in terms of random molecular motion versus directed or coordinated motion. In muscle cells, from organisms as simple as yeast to those as complex as humans, the hydrolysis of ATP provides the driving force for the interactions and conformation of two cellular proteins, myosin and actin. Conformational changes associated with the binding and release of ATP and ADP provide the means by which a coordinated movement of these muscle cells is possible to do mechanical work. 

B) The hydrolysis products remain bound to myosin, and actin is prevented from binding due to the action of one of the light-chain proteins called tropomyosin, which is bound around the myosin. When muscle is stimulated, tropomyosin shifts position, the phosphate group is released, and the head groups on myosin can now reach out to form crossbridges with actin monomers. 

D) ATP is bound again to the myosin, and actin is rapidly released by the breaking of the cross-bridge. 

In summary, interaction between actin and myosin in vertebrate and invertebrate muscle systems requires a critical level of calcium. It is tentatively suggested that interaction between myosin and actin is prevented by blocking sites on actin in the case of vertebrate muscles, whereas in the case of molluscan muscles it is the sites on myosin which are blocked in the absence of calcium. The acidic amino acids seem to be of utmost importance in the regulation process. 

The muscle sarcomere contains the principal contractile proteins myosin and actin (Fig. 3A to C), which on their own can produce force and movement, together with a number of cytoskeletal and regulatory proteins. The latter include titin, C-protein (MyBP-C), tropomyosin, troponin, a-actinin, myomesin, M-protein, and so on. Some of these help to organize the myosin and actin filaments in the sarcomere, some to define the filament lengths and structure, some to regulate activity, and some to modulate the actin-myosin interaction when the muscle is active. 

Figure 8.12 Interaction between myosin and actin (thin and thick filaments) during muscle contraction. (Reproduced by permission from Adelstein RS, Eisenberg E. Regulation and kinetics of the actin-myosin-ATP interaction. Annu Rev Biochem 49 921-956, 1980.)... 

Representation of the four steps in the contractile cycle of muscle showing the association and dissociation of myosin and actin driven by the hydrolysis of... 

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