Tropomyosin interactions

B. The Troponin Complex and the TnT-Tropomyosin Interaction 1. Structure of Troponin... 

Wegner, A. (1979). Equilibrium of the actin-tropomyosin interaction./. Mol. Biol. 131, 839-853. 

Apart from the phosphorylation theory, other regulatory mechanisms have also been suggested for smooth muscle contraction. A thin-filament protein that has been proposed as a regulatory component is caldesmon [102], Purified caldesmon is a potent inhibitor of actin-tropomyosin interaction with myosin. The mechanisms by which calcium removes this inhibition are controversial. Furthermore, phosphorylation of caldesmon by a caldesmon kinase in vitro has also been implicated in this... 

The characteristic stoichiometry of tropomyosin binding, in which one molecule of tropomyosin interacts with approximately 7 actin monomers of F-actin, is the same in skeletal and smooth muscles (Matsumura... 

These drugs mediate an inward current of calcium, possibly due to the inhibition of phosphodiesterase. In addition, they cause a release of intracellular calcium from stores in the cardiac sarcoplasmic reticulum. This increases troponin-tropomyosin interactions, and, consequently, force of contraction. 

Both smooth and skeletal muscle actin filaments are saturated with tropomyosin (Sobieszek and Bremel 1975). Both exhibit the same characteristic stoichiometry of binding of 1 molecule of tropomyosin interacting with 7 monomeric units of F-actin on each of the two strands of F-actin (Hartshorne 1987). The length of tropomyosin molecules (284 amino acids) and their periodicity in smooth and striated muscles is the same (Matsumura and Lin 1982). In both tissues, tropomyosin exists as a dimeric a-helical coil (Caspar et al 1969). Individual tropomyosin molecules bind in an end to end fashion to form a continuous strand on the thin filament that lies along the long-pitch of the double helix formed by the actin monomers (Moore et al 1970, OBrien et al 1971, Spudich et al 1972, Milligan et al 1990). 

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... 

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. 

Tropomyosin and troponin are proteins located in the thin filaments, and together with Ca2+, they regulate the interaction of actin and myosin (Fig. 43-3) [5]. Tropomyosin is an a-helical protein consisting of two polypeptide chains its structure is similar to that of the rod portion of myosin. Troponin is a complex of three proteins. If the tropomyosin-troponin complex is present, actin cannot stimulate the ATPase activity of myosin unless the concentration of free Ca2+ increases substantially, while a system consisting solely of purified actin and myosin does not exhibit any Ca2+ dependence. Thus, the actin-myosin interaction is controlled by Ca2+ in the presence of the regulatory troponin-tropomyosin complex [6]. 

Movement. The interaction between actin and myosin is responsible for muscle contraction and cell movement (see p.332). Myosin (right), with a length of over 150 nm, is among the largest proteins there are. Actin filaments (F-actin) arise due to the polymerization of relatively small protein subunits (G-actin). Along with other proteins, tropomyosin, which is associated with F-actin, controls contraction. 

The vigor of contraction of heart muscle is determined by several processes that lead to the movement of actin and myosin filaments in the cardiac sarcomere (Figure 13-1). Ultimately, contraction results from the interaction of activator calcium (during systole) with the actin-troponin-tropomyosin system, thereby releasing the actin-myosin interaction. This calcium is released from the sarcoplasmic reticulum (SR). The amount released depends on the amount stored in the SR and on the amount of trigger calcium that enters the cell during the plateau of the action potential. 

Averaged helical hydrophobic moment ratios are evaluated in order to assess the potential of amphiphilic regions contributing to the helix-helix interaction responsible for stabilization of tropomyosin dimers. These ratios yield profiles that are higher in the amino-terminal half than in the carboxyl-terminal half of a and p tropomyosin chains. The higher profiles found in the amino-terminal half of a tropomyosin may contribute to the greater stability of the dimer in this region. 

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