Myosin filament structure

In a previous section we mentioned the significance of myosin filament structure. In nematodes two forms of myosin-II, myosin A and B, are required for proper filament stmcture (Epstein, 1988). The two forms of myosin are expressed at the proper time to allow for correct filament assembly. An accessory protein called paramyosin is also required for correct filament assembly. In vertebrate cardiac muscle, there are also two isoforms of myosin-II a-myosin and p-myosin. The proper ratio of these two proteins is of utmost importance for proper muscle activity. The incorrect synthesis of a- and P-myosins results in a severe cardiac disorder known as hypertrophic cardiomyopathy. Genetic transmission of the disease occurs in about 55% of families. The inherited condition is called familial hypertrophic cardiomyopathy (FHC), and this condition is a leading cause of sudden death in young athletes. 

Fig. 18C. (B) Cross-sectional views of the three crowns of the EM 3D map shown in E. (C) Cross-sectional views of the densities between the crowns of the EM 3D map shown in E. (D) Stereo view of the X-ray model of Fig. 18C reconstructed to 50 A resolution. (E) Stereo view of the 3D reconstruction of the myosin filament structure obtained by single particle analysis using the classes shown in Fig. 19C (from Al-Khayat et ai, 2005a). The...

Squire, J. M. (1972). General model of myosin filament structure. II. Myosin filaments and cross-bridge interactions invertebrate striated and insect flight muscles./. Mol. Biol. 72, 125-138. 

Myosin filament structure has been described by Squire et al. (2005). In vertebrate striated muscles the myosin filaments can be described approximately as three-stranded 9/1 helices. The helix pitch is 1287 A, but, because there are three strands and nine subunits in each strand, the structure repeats after C = 1287/3 = 429 A. Figure 12 shows the expected form of the low-angle diffraction pattern from such filaments. The modeling of this structure by X-ray diffraction was described by Squire et al. in terms of the three crowns of heads within each 429 A repeat. The crown repeat of 143 A gives rise to an m = +1 meridional reflection, which has been labeled as the M3 reflection in many muscle studies (as in Fig. 12). The myosin head array also gives rise to layer lines at orders of the repeat of 429 A. The first myosin layer line (ML1) is at 1/429 A-1, the second (ML2) at 2/429 = 1/ 214.5 A-1, and so on. The M3 reflection occurs on the third layer line at 3/429 = 1/143 A-1. 

Fig. 4. Myosin filament structure. Dit rams of myosin monomer packing in non-helical side-polar and helical bipolar filaments. For simplicity, only one myosin head per monomer is shown. A bare zone is observed at the center of the bi-polar filament, and at each end of the side-polar filament...

Figure 14.17 A sequence of events combining the swinging cross-bridge model of actin and myosin filament sliding with structural data of myosin with and without bound nucleotides.

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. 

The structure of the contractile apparatus of smooth muscle at the next higher level is also characteristically different from other muscles. The concentrations of actin and myosin in smooth muscle are about three times higher for actin and four times lower for myosin than in skeletal muscle. Correspondingly, in smooth muscle the ratio of the numbers of moles of actin to moles of myosin, and the ratio of the number of actin filaments to those of myosin filaments, are about 12 times larger than for other muscles. Thus, the arrangements of the two sets of filaments are bound to be quite different just on the basis of numbers of actin and myosin... 

The increment to force during activation. Presumably, the structures which maintain the resting force are not those which are activated or even changed following a stimulus. Therefore, activation involves the parallel addition of a nascent force resulting from the emergent interaction of the actin and myosin filaments. Active force is therefore an incremental force added to the resting force. This is a fundamental assumption of almost all analyses of contraction from A.V. Hill onward. 

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. 

The superstructure of smooth muscle actin filaments is differentiated from those of striated muscle by the absence of the troponins and the lateral organization by association of the filaments with dense bodies instead of with the Z-line. How these differences are encoded is again not at all clear. However, the myofibrillar structure and the alignment of the alternating actin and myosin filaments is apparently due primarily to dense bodies and the actin-actinin macrostructures. As the bent dumbbell shaped actins assemble into filaments they are all oriented in the same direction. The S-1 fragments of myosin will bind to actin filaments in vitro and in... 

Because there are no sarcomeres in smooth muscle, there are no Z lines. Instead, the actin filaments are attached to dense bodies. These structures, which contain the same protein as Z lines, are positioned throughout the cytoplasm of the smooth muscle cell as well as attached to the internal surface of the plasma membrane. Myosin filaments are associated with the actin filaments, forming contractile bundles oriented in a diagonal manner. This arrangement forms a diamond-shaped lattice of contractile elements throughout the cytoplasm. Consequently, the interaction of actin and myosin during contraction causes the cell to become shorter and wider. 

The internal physical flow along filamentous structures, made from actin, myosin, tubulin and similar proteins in later cells, can be of small or large molecules, or even of vesicles, so that movements on internal surfaces become more... 

Fibrous proteins represent a substantial subset of the human proteome. They include the filamentous structures found in animal hair that act as a protective and thermoregulatory outer material. They are responsible for specifying much of an animal s skeleton, and connective tissues such as tendon, skin, bone, cornea and cartilage all play an important role in this regard. Fibrous proteins are frequently crucial in locomotion and are epitomised by the muscle proteins myosin and tropomyosin and by elastic structures like titin. Yet again the fibrous proteins include filamentous assemblies, such as actin filaments and microtubules, where these provide supporting structures and tracks for the action of a variety of molecular motors. 

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