Muscle tropomyosin

Proteins can be broadly classified into fibrous and globular. Many fibrous proteins serve a stmctural role (11). CC-Keratin has been described. Fibroin, the primary protein in silk, has -sheets packed one on top of another. CoUagen, found in connective tissue, has a triple-hehcal stmcture. Other fibrous proteins have a motile function. Skeletal muscle fibers are made up of thick filaments consisting of the protein myosin, and thin filaments consisting of actin, troponin, and tropomyosin. Muscle contraction is achieved when these filaments sHde past each other. Microtubules and flagellin are proteins responsible for the motion of ciUa and bacterial dageUa. 

Ansari, S., El-Mezgueldi, M., and Marston, S. (2003). Cooperative inhibition of actin filaments in the absence of tropomyosin./. Muscle Res. Cell. Motil. 24, 513-520. 

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. 

Muscle contraction is initiated by a signal from a motor nerve. This triggers an action potential, which is propagated along the muscle plasma membrane to the T-tubule system and the sarcotubular reticulum, where a sudden large electrically excited release of Ca " into the cytosol occurs. Accessory proteins closely associated with actin (troponins T, I, and C) together with tropomyosin mediate the Ca -dependent motor command within the sarcomere. Other accessory proteins (titin, nebulin, myomesin, etc.) serve to provide the myofibril with both stability... 

Tropomyosin is thought to lie in the groove formed between the associated actin strands. The sites at which the myosin crossbridges attach are affected by the relationship between tropomyosin and the actin strands. The role of tropomyosin in smooth muscle is completely undefined while in striated muscle it is clearly involved in the activation of contraction. The difference is made clear by the absence from smooth muscle of the protein, troponin, which in striated muscle provides the binding site for the triggering calcium. 

Both the thick and thin filaments contain other proteins. For example, the thick filament contains titin (molecular weight about 3,000,000) and the thin filament contains nebulin (although not in cardiac muscle), and the regulatory proteins troponin (molecular weight about 33,000) and tropomyosin (molecular weight about 70,000). Nebulin and titin are thought to be ruler proteins, that is, they determine the overall length of the thin and the thick filament, respectively. The... 

CTien contraction of muscle is stimulated (via events involving Ca +, troponin, tropomyosin, and actin, which are described below), actin becomes accessible and the S-1 head of myosin finds it, binds it, and forms the actin-myosin-ADP-P complex indicated. 

Tropomyosin the Troponin Complex Present in Thin Filaments Perform Key Functions in Striated Muscle... 

In striated muscle, there are two other proteins that are minor in terms of their mass but important in terms of their function. Tropomyosin is a fibrous molecule that consists of two chains, alpha and beta, that attach to F-actin in the groove between its filaments (Figure 49-3). Tropomyosin is present in all muscular and muscle-fike structures. The troponin complex is unique to striated muscle and consists of three polypeptides. Troponin T (TpT) binds to tropomyosin as well as to the other two troponin components. Troponin I (Tpl) inhibits the F-actin-myosin interaction and also binds to the other components of troponin. Troponin C (TpC) is a calcium-binding polypeptide that is structurally and functionally analogous to calmodulin, an important calcium-binding protein widely distributed in nature. Four molecules of calcium ion are bound per molecule of troponin C or calmodulin, and both molecules have a molecular mass of 17 kDa. 

Thus, Ca " controls skeletal muscle contraction and relaxation by an allosteric mechanism mediated by TpC, Tpl, TpT, tropomyosin, and F-actin. 

The general picture of muscle contraction in the heart resembles that of skeletal muscle. Cardiac muscle, like skeletal muscle, is striated and uses the actin-myosin-tropomyosin-troponin system described above. Unlike skeletal muscle, cardiac muscle exhibits intrinsic rhyth-micity, and individual myocytes communicate with each other because of its syncytial nature. The T tubular system is more developed in cardiac muscle, whereas the sarcoplasmic reticulum is less extensive and consequently the intracellular supply of Ca for contraction is less. Cardiac muscle thus relies on extracellular Ca for contraction if isolated cardiac muscle is deprived of Ca, it ceases to beat within approximately 1 minute, whereas skeletal muscle can continue to contract without an extraceUular source of Ca +. Cyclic AMP plays a more prominent role in cardiac than in skeletal muscle. It modulates intracellular levels of Ca through the activation of protein kinases these enzymes phosphorylate various transport proteins in the sarcolemma and sarcoplasmic reticulum and also in the troponin-tropomyosin regulatory complex, affecting intracellular levels of Ca or responses to it. There is a rough correlation between the phosphorylation of Tpl and the increased contraction of cardiac muscle induced by catecholamines. This may account for the inotropic effects (increased contractility) of P-adrenergic compounds on the heart. Some differences among skeletal, cardiac, and smooth muscle are summarized in... 

While all muscles contain actin, myosin, and tropomyosin, only vertebrate striated muscles contain the troponin system. Thus, the mechanisms that regulate contraction must differ in various contractile systems. 

Smooth muscles have molecular structures similar to those in striated muscle, but the sarcomeres are not aligned so as to generate the striated appearance. Smooth muscles contain a-actinin and tropomyosin molecules, as do skeletal muscles. They do not have the troponin system, and the fight chains of smooth muscle myosin molecules differ from those of striated muscle myosin. Regulation of smooth muscle contraction is myosin-based, unlike striated muscle, which is actin-based. However, like striated muscle, smooth muscle contraction is regulated by Ca. ... 

When smooth muscle myosin is bound to F-actin in the absence of other muscle proteins such as tropomyosin, there is no detectable ATPase activity. This absence of activity is quite unlike the situation described for striated muscle myosin and F-actin, which has abundant ATPase activity. Smooth muscle myosin contains fight chains that prevent the binding of the myosin head to F-actin they must be phosphorylated before they allow F-actin to activate myosin ATPase. The ATPase activity then attained hydrolyzes ATP about tenfold more slowly than the corresponding activity in skeletal muscle. The phosphate on the myosin fight chains may form a chelate with the Ca bound to the tropomyosin-TpC-actin complex, leading to an increased rate of formation of cross-bridges between the myosin heads and actin. The phosphorylation of fight chains initiates the attachment-detachment contraction cycle of smooth muscle. 

Proteins of muscle filaments Actin Myosin Tropomyosin Troponin (Tpl,TpT,TpC) Actin Myosin Tropomyosin... 

The myofibrils of skeletal muscle contain thick and thin filaments. The thick filaments contain myosin. The thin filaments contain actin, tropomyosin, and the troponin complex (troponins T, I, and C). 

When the action potentials in the alpha motor neuron cease, stimulation of muscle fiber is ended. Ca++ ions are pumped back into the sarcoplasmic reticulum and troponin and tropomyosin return to their original positions. As a result, the myosin-binding sites on the actin are covered once again. The thin filaments return passively to their original positions, resulting in muscle relaxation. 

In skeletal muscle, calcium binds to troponin and causes the repositioning of tropomyosin. As a result, the myosin-binding sites on the actin become uncovered and crossbridge cycling takes place. Although an increase in cytosolic calcium is also needed in smooth muscle, its role in the mechanism of contraction is very different. Three major steps are involved in smooth muscle contraction ... 

In addition to actin and myosin, other proteins are found in the two sets of filaments. Tropomyosin and a complex of three subunits collectively called troponin are present in the thin filaments and play an important role in the regulation of muscle contraction. Although the proteins constituting the M and the Z bands have not been fully characterized, they include a-actinin and desmin as well as the enzyme creatine kinase, together with other proteins. A continuous elastic network of proteins, such as connectin, surround the actin and myosin filaments, providing muscle with a parallel passive elastic element. Actin forms the backbone of the thin filaments [4]. The thin... 

Zot, A. S. and Potter, J. D. Structural aspects of troponin-tropomyosin regulation of skeletal muscle contraction. Annu. Rev. Biophys. Biophys. Chem. 16 535-560,1987. 

Contractile proteins which form the myofibrils are of two types myosin ( thick filaments each approximately 12 nm in diameter and 1.5 (im long) and actin ( thin filaments 6nm diameter and 1 (Am in length). These two proteins are found not only in muscle cells but widely throughout tissues being part of the cytoskeleton of all cell types. Filamentous actin (F-actin) is a polymer composed of two entwined chains each composed of globular actin (G-actin) monomers. Skeletal muscle F-actin has associated with it two accessory proteins, tropomyosin and troponin complex which are not found in smooth muscle, and which act to regulate the contraction cycle (Figure 7.1). 

Tropomyosin is a fibrous molecule which twists around the F-actin strands. The troponin (Tn) complex is composed of three proteins Tnl (I = inhibitory) which prevents myosin binding to actin in the resting muscle, TnT which binds tropomyosin and TnC (C for calcium-binding). Cardiac muscle troponins are different from those of skeletal muscle and are designated cTnl, cTnT and cTnC. 

ATP is used not only to power muscle contraction, but also to re-establish the resting state of the cell. At the end of the contraction cycle, calcium must be transported back into the sarcoplasmic reticulum, a process which is ATP driven by an active pump mechanism. Additionally, an active sodium-potassium ATPase pump is required to reset the membrane potential by extruding sodium from the sarcoplasm after each wave of depolarization. When cytoplasmic Ca2- falls, tropomyosin takes up its original position on the actin and prevents myosin binding and the muscle relaxes. Once back in the sarcoplasmic reticulum, calcium binds with a protein called calsequestrin, where it remains until the muscle is again stimulated by a neural impulse leading to calcium release into the cytosol and the cycle repeats. 

In smooth muscle, caldesmon plays an analogous role to that of troponin in striated muscle in that it blocks the myosin binding sites. The CaCM complex removes caldesmon from its binding on the thin actin filaments allowing tropomyosin to reposition in the helical grooves of F-actin leading to myosin ATP ase activation. 

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