Tropomyosin structure

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. 

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. 

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

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. ... 

Ishi, Y., and Lehrer, S.S. (1986) Effects of the state of the succinimido-ring on the fluorescence and structural properties of pyrene maleimide-labeled an-tropomyosin. Biophys./. 50, 75-80. 

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]. 

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. 

Figure 19-9 Stereoscopic ribbon drawing of the proposed structure of a thin actin filament with tropomyosin coiled-coils bound on opposing sides.124 Five actin nomomers are assembled in the structure as is also illustrated in Fig. 7-10. From Lorenz et al.125 Courtesy of Michael Lorenz.

A molecular view of muscle structure, (a) Segment of actin-tropomyosin-troponin. 

The protein tropomyosin (TM) is composed of two identical chains of a helix (see table 5.1) that are in turn twisted around each other in a helical structure. Consider the average amino acid residue weight to be 105 daltons and use typical a-helix dimensions (fig. 4.4) to calculate the length of each chain in TM. Explain any discrepancy observed between the calculated length and the observed length of 360 A. 

By examining the amino add sequence of tropomyosin, the smallest and simplest proteins postulated at the time 1819 to contain the coiled-coil motif, we identified the hydrophobic repeat responsible for the formation and stabilization of the coiled-coil structure. 18 A coiled coil can be considered as a repeating heptad of seven amino acid residues a-b-c-d-e-f-g, where positions a and d are occupied by hydrophobic residues. This 3-4 (or 4-3) hydro-... 

Parry, D. A. D., and Squire, J. M. (1973). The structural role of tropomyosin in muscle regulation Analysis of the X-ray diffraction patterns from relaxed and contracting muscles. /. Mol. Biol. 37, 33—55. 

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... 

Historically, coiled coils were identified with long fibrous molecules, from which their structural properties had been determined. Fiber diffraction studies on proteins of the k-m-e-f class were highly successful, initially on dried specimens but later also on native samples (Cohen and Holmes, 1963). However, these proteins turned out to be very difficult to analyze by high-resolution X-ray crystallography for the same reasons that made them so amenable to fiber diffraction—their tendency to aggregate into fibers rather than crystals and the extreme dimensions of their asymmetric units. It took decades to obtain a working structure for tropomyosin [at 15 A resolution (Phillips et al., 1986) at 9 A (Whitby et al.,... 

Li, Y., Mui, S., Brown, J. H., Strand, J., Reshetnikova, L., Tobacman, L. S., and Cohen, C. (2002). The crystal structure of the C-terminal fragment of striated-muscle a-tropomyosin reveals a key troponin T recognition site. Proc. Natl. Acad. Sci. 99, 7378-7383. 

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