Thin filament proteins skeletal muscle

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. 

The principal molecular constituent of thin filaments is actin. Actin has been highly conserved during the course of evolution and is present in all eukaryotes, including single-celled organisms such as yeasts. Actin was first extracted and purified from skeletal muscle, where it forms the thin filaments of sarcomeres. It also is the main contractile protein of smooth muscle. Refined techniques for the detection of small amounts of actin (e.g., immunofluorescence microscopy, gel electrophoresis, and EM cytochemistry) subsequently confirmed the presence of actin in a great variety of nonmuscle cells. Muscle and nonmuscle actins are encoded by different genes and are isoforms. 

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). 

The major allergen of molluscan shellfish is tropomyosin, a muscle protein. The term major allergen is used to define proteins that elicit IgE binding in the sera of half or more of patienfs wifh allergies to the specific source (Metcalfe et ah, 1996). Tropomyosin is a ubiquitous muscle protein in all animals. Tropomyosin is a 34- to 36-kDa protein that is highly water soluble and heat stable as evidenced by the fact that tropomyosin can be isolated from fhe water used to boil shrimp (Daul et ah, 1994). Tropomyosin can actually be found in bofh muscle and many nonmuscle cells in animals. In muscle cells, tropomyosin is associated with the thin filaments in muscle and plays a role in the contractile activity of muscle cells. In nonmuscle cells, tropomyosin is found in microfilaments but its fimction is less well imderstood. Tropomyosins are present in all eukaryotic cells. Different isoforms of tropomyosin are found in different types of muscle cells (skeletal, cardiac, smooth), brain, fibroblasts, and other nonmuscle cells. While these tropomyosins are highly homologous, small differences do exist in their... 

Actin and the thin filaments. There are at least six forms of actin in adult mammalian tissues a-cardiac, a-skeletal muscle, a- and y-smooth muscle, P- and y-cytoplasmic.87 89 All of them are closely homologous, e.g., the 42-kDa a-skeletal muscle actin differs in only 4 of 375 residues from the a-cardiac form and only in 6 residues from the y-smooth form. In almost all organisms actins contain one residue of N5-methylhistidine at position 73.87/88/90 Actin is an unusual protein in that... 

Figure 8.11 Aggregation of F-actin, tropomyosin and troponin to form the thin filaments of myofibrils. (Reproduced by permission from Ohtsuki I, Maruyama K, Ebashi S. Regulatory and cytoskeletal protein of vertebrate skeletal muscle. Adv Prot Chem 38 1— 60, 1986.)...

A protein with a similar dumbell shape and structure is troponin C of skeletal muscles. Troponin C binds to a complex of proteins that assemble on the thin actin filaments of muscle fibers and control con-trachon in response to changes in the calcium ion con-centrahon (Chapter 19). Other proteins that contain EF-hand mohfs and are therefore responsive to Ca + include spectrin of cell membranes, clathrin light chains from coated vesicles, the extracellular osteonectin of bones and teeth, ° and a birch pollen anhgen. 2 Another group of 17 or more small SlOO EF-hand proteins play a variety of other roles. One of these, which has a high affinity for Zn +, has been named psoriasin because of its 5-fold or greater... 

Another very long protein (nebulin) is associated with the thin filaments. Nebulin has a molecular weight of about 700,000. An abundant protein in skeletal muscle, nebulin extends from either side of the Z-disks along the entire length of the thin filaments. It may serve as a template for thin-filament assembly, and may interact with tropomyosin, and also may have a regulatory role. 

The answer is b. (Murray, pp 48-62. Scriver, pp 3-45. Sack, pp 1-3. Wilson, pp 101-120.) Two kinds of interacting protein filaments are found in skeletal muscle. Thick filaments 15 nm in diameter contain primarily myosin. Thin filaments 7 nm in diameter are composed of actin, troponin, and tropomyosin. The thick and thin filaments slide past one another during muscle contraction. Myosin is an ATPase that binds to thin filaments during contraction, ot-actinin can be found in the Z line. 

Schematic diagram of the organization of skeletal muscle thin filament, showing the position of tropo-myosin and the troponin complex on the actin filament. The binding of Ca " to TnC, the calcium-binding subunit of the troponin complex, removes Tnl, the inhibitory subunit, from actin and thus permits an interaction with a specialized protein, myosin, on neighboring thick muscle filaments (not shown). An ATP-driven conformation change in the myosin head group makes the thick and thin filaments move relative to one another, so that muscle contraction occurs.

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