Myosin/ tropomyosin

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... 

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

A second widely used sequence-based approach relies on matrices of residue frequencies, pioneered by Parry (1982). He showed that the residue distribution at the seven heptad positions of the putative coiled-coil segments of myosin, tropomyosin, o-keratin, and hemaglutinin are asymmetric, and proposed a method by which the residue frequencies could be used to predict whether a sequence of unknown structure would form a coiled coil. This approach was implemented with modifications in... 

Calponin" Actin Myosin Tropomyosin V max (%) (%) ratio CP/A motility (pM CP) Reference... 

Muscle proteins have traditionally been grouped into three categories based on their solubility the sarcoplasmic proteins (consisting mainly of enzymes), myofibrillar proteins (actin, myosin, tropomyosin, troponin, etc.) and connective tissue (mainly collagen). The mixture of myosin, actin, tropomyosin, troponins and other myofibrillar proteins is called actomyosin (AM). Myofibrillar proteins contribute significantly to the technological properties of fish and meat [1-2,5-8]. 

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. 

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. 

Troponin C Troponin I Troponin T Minor M protein 18 21 31 165 2 M line Ca binding Inhibits actin-myosin interaction Binds to tropomyosin Binds to myosin... 

Bundles of parallel actin filaments with uniform polarity. The microvilli of intestinal epithelial cells (enterocytes) are packed with actin filaments that are attached to the overlying plasma membrane through a complex composed of a 110-kD protein and calmodulin. The actin filaments are attached to each other through fimbrin (68 kD) and villin (95 kD). The actin bundles that emerge out of the roots of microvilli disperse horizontally to form a filamentous complex, the terminal web, in which several cytoskeletal proteins, spectrin (fodrin), myosin, actinin, and tropomyosin are present. Actin in the terminal web also forms a peripheral ring, which is associated with the plasma membrane on the lateral surfaces of the enterocyte (see Figure 5, p. 24). 

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. 

The thin filament (about 7 nm in diameter) fies in the 1 band and extends into the A band but not into its H zone (Figure 49-2). Thin filaments contain the proteins actin, tropomyosin, and troponin (Figure 49-3). In the A band, the thin filaments are arranged around the thick (myosin) filament as a secondary hexagonal array. Each thin filament lies symmetrically between three thick filaments (Figure 49-2, center mid cross-... 

Figure 49-3. Schematic representation of the thin fiiament, showing the spatiai configuration of its three major protein components actin, myosin, and tropomyosin. The upper panei shows individual molecules of G-actin. The middle panel shows actin monomers assembled into F-actin. Individual molecules of tropomyosin (two strands wound around one another) and of troponin (made up of its three subunits) are also shown. The lower panel shows the assembled thin filament, consisting of F-actin, tropomyosin, and the three subunits of troponin (TpC, Tpl, andTpT).

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. 

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. 

When the sarcolemma is excited by a nerve impulse, the signal is transmitted into the T tubule system and a release channel in the nearby sarcoplasmic reticulum opens, releasing Ca + from the sarcoplasmic reticulum into the sarcoplasm. The concentration of Ca in the sarcoplasm rises rapidly to 10 mol/L. The Ca -binding sites on TpC in the thin filament are quickly occupied by Ca +. The TpC-4Ca + interacts with Tpl and TpT to alter their interaction with tropomyosin. Accordingly, tropomyosin moves out of the way or alters the conformation of F-actin so that the myosin head-ADP-P (Figure 49-6) can interact with F-actin to start the contraction cycle. 

Relaxation occurs when sarcoplasmic Ca falls below 10 mol/L owing to its resequestration into the sarcoplasmic reticulum by Ca ATPase. TpC.dCa thus loses its Ca. Consequently, troponin, via interaction with tropomyosin, inhibits further myosin head and F-actin interaction, and in the presence of ATP the myosin head detaches from the F-actin. 

Abnormalities of myocardial contractile and structural proteins P-Myosin heavy chains, troponin, tropomyosin, dystrophin... 

Figure 49-13. Simplified scheme of the causation of familial hypertrophic cardiomyopathy (MIM 192600) due to mutations in the gene encoding fi-myosin heavy chain. Mutations in genes encoding other proteins, such as the troponins, tropomyosin, and cardiac myosin-binding protein C can also cause this condition. Mutations in genes encoding yet other proteins (eg, dystrophin) are involved in the causation of dilated cardiomyopathy.

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. 

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