Muscle Titin

Trombitas, K., Greaser, M., and French, G. (1998a). PEVK extension of human soleus muscle titin revealed by immunolabeling with the anti-titin antibody 9D10./. Struct. Biol. 122, 188-196. 

Several hypotheses could explain the large apparent size of VERL. Like muscle titin, VERL could be encoded by a single giant mRNA. VERL subunits could be linked together after their synthesis by a transglutaminase reaction. VERL s size... 

Improta et al., 1996] Improta, S., Politou, A., and Pasture, A. Immunoglobulinlike modules from titin I-band extensible components of muscle elasticity. Structure. 4 (1996) 323-337... 

Maruyama, 1997] Maruyama, K. Connectin/titin, a giant elastic protein of muscle. FASEB J. 11 (1997) 341-345... 

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... 

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... 

A number of additional proteins play various roles in the structure and function of muscle. They include titin (the largest protein known), nebufin, a-actinin, desmin, dystrophin, and calcineurin. Some properties of these proteins are summarized in Table 49-2. 

Titin Reaches from the Z line to the M line Largest protein in body. Role in relaxation of muscle. 

Some proteins may be very large, indeed. Titin, for example, a muscle protein and the largest known protein, includes in its molecule over 26,000 combined amino acid units. 

Protein domains are the common currency of protein structure and function. Protein domains are discrete structural units that fold up to form a compact globular shape. Experiments on protein structure and function have been greatly aided by consideration of the modular nature of proteins. This has allowed very large proteins to be studied. The expression of individual domains has allowed the intractable giant muscle protein titin to be structurally studied (Pfuhl and Pastore, 1995). Protein domains can be found in a variety of contexts, (Fig. 1), in association with a range of unrelated domains and in a variety of orders. Ultimately protein domains are defined at the level of three-dimensional structure however, many protein domains have been described at the level of sequence. The success of sequence-based methods has been demonstrated by numerous confirmations, by elucidation of the three-dimensional structure of the domain. 

In addition to the above proteins, a number of other proteins are also typical of muscle—including titin (the largest known protein), a- and j3-actinin, desmin, and vimentin. 

Labeit S, Kolmerer B. Titins giant proteins in charge of muscle ultrastmcture and elasticity. Science 1995 270 293-296. 

Li H, Linke WA, Oberhauser AF, Carrion-Vazquez M, Kerkvliet JG, Lu H, Marszalek PE, Fernandez JM. Reverse engineering of the giant muscle protein titin. Nature (Lond) 2002 418 998-1002. 

Wang K. Titin/connectin and nebulin giant protein rulers of muscle structure and function. Adv Biophys 1996 33 123-134. 

How long are the polypeptide chains in proteins As Table 3-2 shows, lengths vary considerably. Human cytochrome c has 104 amino acid residues linked in a single chain bovine chymotrypsinogen has 245 residues. At the extreme is titin, a constituent of vertebrate muscle, which has nearly 27,000 amino acid residues and a molecular weight of about 3,000,000. The vast majority of naturally occurring proteins are much smaller than this, containing fewer than 2,000 amino acid residues. 

These domains, which are found in the muscle protein titin as well as in fibronectin, resemble immunoglobulin domains but lack disulfide bridges. From Erickson.1173 Figure courtesy of Flarold P. Erickson. 

Figure 19-6 (A) The structure of a typical sarcomere of skeletal muscle. The longitudinal section depicted corresponds to that of the electron micrograph, Fig. 19-7A. The titin molecules in their probable positions are colored green. The heads of only a fraction of the myosin molecules are shown protruding toward the thin actin filaments with which they interact.

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