Myosin filaments in muscle

The structure and arrangement of the actin and myosin filaments in muscle. During muscle contraction the cyclic interaction of myosin crossbridges with actin filaments draws the actin filaments across the myosin filaments. 

Because muscle fibers in males are thicker than those found in females, these muscles are larger and stronger, even without the benefit of resistance training. This enlargement is due to effects of testosterone, a sex hormone found primarily in males. Testosterone promotes the synthesis of actin and myosin filaments in muscle fibers. 

In addition to the highly organized arrangement of actin and myosin filaments in muscle (discussed in detail in Squire et al., 2005), there are also highly organized arrays of microtubules in the cilia and flagella of eukaryotes that either pass fluid across the cell surface or act as the propellers for spermatazoa (Fig. IB). Ordered arrays of actin also occur in microvilli on the surfaces of cells from the brush border of intestinal epithelia. Here, the highly cross-linked actin arrays appear to be tensioned by interaction with myosin at the bases of the microvilli in the terminal web (Fig. 2B). 

First, in the striated muscles, the cross-sectional organization of filaments is highly ordered in a hexagonal pattern commensurate with the ratio of actin to myosin filaments and the distribution of active myosin heads, S-1 segments, helically every 60 degrees around the myosin filament. In smooth muscle, with perhaps 13 actin filaments per myosin filament, many actin filaments appear to be ranked in layers around myosin filaments. It is not known how the more distant actin filaments participate in contraction. 

Organization into macromolecular structures. There are no apparent templates necessary for the assembly of muscle filaments. The association of the component proteins in vitro is spontaneous, stable, and relatively quick. Filaments will form in vitro from the myosins or actins from all three kinds of muscle. Yet in vitro smooth muscle myosin filaments are found to be stable only in solutions somewhat different from in vivo conditions. The organizing principles which govern the assembly of myosin filaments in smooth muscle are not well understood. It is clear, however, a filament is a sturdy structure and that individual myosin molecules go in and out of filaments whose structure remains in a functional steady-state. As described above, the crossbridges sticking out of one side of a smooth muscle myosin filament are all oriented and presumably all pull on the actin filament in one direction along the filament axis, while on the other side the crossbridges all point and pull in the opposite direction. The complement of minor proteins involved in the structure of the smooth muscle myosin filament is unknown, albeit not the same as that of skeletal muscle since C-protein and M-protein are absent. 

In addition to actin and myosin, other proteins are found in the two sets of filaments. Tropomyosin and a complex of three subunits collectively called troponin are present in the thin filaments and play an important role in the regulation of muscle contraction. Although the proteins constituting the M and the Z bands have not been fully characterized, they include a-actinin and desmin as well as the enzyme creatine kinase, together with other proteins. A continuous elastic network of proteins, such as connectin, surround the actin and myosin filaments, providing muscle with a parallel passive elastic element. Actin forms the backbone of the thin filaments [4]. The thin... 

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. 

The A-band lattices in different kinds of striated muscles have distinct arrangements. As shown in Fig. 3 and reproduced in simpler form in Fig. 10A and B, vertebrate striated muscle A-bands have actin filaments at the trigonal points of the hexagonal myosin filament array. As discussed prevously, this array also occurs in two types, the simple lattice and superlattice. The ratio of actin filaments to myosin filaments in each unit cell is 2 1. In both cases the center-to-center distance between adjacent myosin filaments is 70 A, but this varies as a function of overlap, becoming smaller as the sarcomere lengthens, giving an almost constant volume to the sarcomere (April et al, 1971). 

A typical low-angle diffraction pattern from relaxed bony fish muscle is shown in Fig. 4B. Much of the intensity that is seen comes from the organization of the myosin heads on the myosin filaments in the resting state (probably mainly MADP.Pi). We know that the myosin heads lie approximately on three co-axial helices of subunit translation 143 A and repeat 429 A. This is most easily represented by the radial net shown in Fig. 16B-D. The radial net in D is like an opened-out surface view of the filament in B. Here the helical tracks become straight lines, and the black blobs represent the origins on the myosin filament surface of the pairs of myosin heads in each myosin molecule. From early studies it is known that the three crowns within the 429 A repeat are not exactly the same and that there is a perturbation. 

Fig. 27. Radial net of various crossbridge lattices from different species along with their corresponding computed Fourier transform. The myosin filament is three-stranded in (A) vertebrate muscle, four-stranded in invertebrates (B and C), and seven-stranded in scallop muscle (D). This figure shows the similarity of the surface lattices of the myosin head origins on the myosin filaments in different muscles although the myosin heads have different slew, tilt, and rotations. Images were created using the program HELIX (Knupp and Squire, 2004).

Fig. 28. Classification of crossbridge configurations in myosin filaments in different muscles. In each case, the axial separation is 143-145 A and the lateral separation is 120-150 A. There are three main classes (A) Class I, where the interaction is between heads of the same molecule as in vertebrate striated muscles (B) Class II, where interaction occurs between heads of adjacent myosin molecules in the same crown, as seen in insect (Lethocerus) flight muscles and (C) Glass III, where the interaction appears to be between heads in different crowns, as seen in tarantula and Limulus.

Lowy, J., Poulsen, F. R., and Vibert, P. J. (1970). Myosin filaments in vertebrate smooth muscle. Nature 225, 1053-1054. 

It was shown in Fig. 27 of Squire et al. (this volume) that the myosin filaments in different muscle types, particularly in invertebrate muscles, have their heads arranged on different surface lattices. There can be different numbers of helical strands and also different axial repeats. However, in all of these other cases the head arrays appear to be perfectly helical. The vertebrate striated muscle myosin filaments are different in that their heads do not lie on perfect helical tracks there is a perturbation (described in Squire et al., this volume, see Fig. 20) that makes the three crowns within a 429 A repeat nonequivalent. This shows up very obviously in the X-ray diffraction patterns from vertebrate striated muscles. If the structure was helical, meridional reflections would be expected to occur only at positions where m = 0, 1, 2, etc., that is, at multiples of 3/429 A-1. In fact, meridional reflections are observed on all of the first few orders of the 429 A repeat, in particular with a strong peak on the second myosin layer line at 214.5 A (M2), and with others at M4, M5, M7, and so on. These are all indications that the helix is not quite perfect. 

The reason for this perturbation could be that the myosin filaments in vertebrate striated muscles carry titin, which has a repeating pattern along it which itself probably has a 429 A spacing, and C-protein (MyBP-C), which in the G-zone region of the A-band appears to label every third crown level. Squire et al. (2003d) showed that the outer, N-terminal, end of C-protein could also bind to actin, in addition to the C-terminal part binding to myosin and to titin, and this may be why there are particular features of the X-ray pattern from striated muscles with an apparent... 

Huxley, H. E., Stewart, A., Sosa, H., and Irving, T. (1994). X-ray diffraction measurements of the extensibility of actin and myosin filaments in contracting muscle. Biophys.J. 67, 2411-2421. 

Actin and myosin fibers or filaments make possible the contraction of muscles. Actin and myosin fibers in muscle lie side by side and react chemically, sliding together and apart to shorten and lengthen in response to energy from adenosine triphosphate. 

The interaction between actin and myosin filaments in the A-band of the sarcomere is responsible for the muscle contraction (shding-fllament model). 

Fig. 15.1. Schematic illustration of the muscle. The force generating unit is the sarcomere with a length of about 2 tm. Contraction is caused by the myosin and actin filaments. Titin spans the whole half-sarcomere, keeps the myosin filaments in place and provides the muscle with its passive elasticity. At the M-line, where titin is cross-linked, the titin kinase is integrated with its surrounding and globular Ig and Fn domains. This position is ideal to detect the imbalances between neighboring filaments...

To further illustrate the properties of motor proteins, we consider myosin II, which moves along actln filaments in muscle cells during contraction. Other types of myosin can transport vesicles along actin filaments in the cytoskeleton. Myosin II and other members of the myosin superfamily are composed of one or two heavy chains and several light chains. The heavy chains are organized into three structurally and functionally different types of domains (Figure 3-24a). 

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