A-Myosin

Figure 14.12 The swinging cross-bridge model of muscle contraction driven by ATP hydrolysis, (a) A myosin cross-bridge (green) binds tightly in a 45 conformation to actin (red), (b) The myosin cross-bridge is released from the actin and undergoes a conformational change to a 90 conformation (c), which then rebinds to actin (d). The myosin cross-bridge then reverts back to its 45° conformation (a), causing the actin and myosin filaments to slide past each other. This whole cycle is then repeated.

FIGURE 17.17 All axial view of the two-stranded, a-helical coiled coll of a myosin tall. Hydrophobic residues a and d of the seven-resldne repeat sequence align to form a hydrophobic core. Residues b, c, and f face the outer surface of the colled coll and are typically Ionic. 

The shortening of a sarcomere (Eigure 17.22) involves sliding motions in opposing directions at the two ends of a myosin thick filament. Net sliding motions in a specific direction occur because the thin and thick filaments both have... 

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. 

Lillie, S.H., Brown, S.S. (1992). Suppression of a myosin defect by a kinsein-related gene. Nature 356, 358-361. 

In his theory, A.F. Huxley suggested that a myosin crossbridge attaches to actin and produces an amount of force which is proportional to the amount of strain on the crossbridge, that is to the amount by which it is distorted (Figure 5). He also suggested that crossbridges were only able to attach over a range of preferred distortions. From these basic ideas he derived mathematical expressions for force... 

Figure 49-4. Diagram of a myosin moiecuie showing the two intertwined a-heiices (fibrous portion), the giobuiar region or head (G),the iight chains (L), and the effects of proteoiytic cieavage by trypsin and papain. The giobuiar region (myosin head) contains an actin-binding site and an L chain-binding site and aiso attaches to the remainder of the myosin moiecuie.

Smooth muscle sarcoplasm contains a myosin light chain kinase that is calcium-dependent. The Ca activation of myosin fight chain kinase requires binding of calmodulin-4Ca to its kinase subunit (Figure 49-14). 

Thick filaments. Each thick filament contains 200 to 300 myosin molecules. Each myosin molecule is made up of two identical subunits shaped like golf clubs two long shafts wound together with a myosin head, or crossbridge, on the end of each. These molecules are arranged so that the shafts are bundled together and oriented toward the center of the thick filament. The myosin heads project outward from either end of the thick filament (see Figure 11.1, panel a). 

Liu P, Hajra A et al. Fusion between transcription factor CBF beta/PEBP2 beta and a myosin heavy chain in acute myeloid leukemia. Science 1993 261 1041-1044. 

Two other myosin types have been implicated in hearing and vestibular function [62]. The defect in the Snell s waltzer mouse was found to be a mutation in a myosin VI gene that produces degeneration of the cochlea and vestibular apparatus. Myosin VI is localized to the cuticular plate of the hair cell under stereocilia. Similarly, mutations in a myosin VII gene are responsible for the shaker-1 mouse and several human genetic deafness disorders. This myosin, myosin Vila, is found in a band near the base of the stereocilia distinct from distributions of myosin ip and myosin VI. 

Microfilaments of F actin traverse the microvilli in ordered bundles. The microfila-ments are attached to each other by actin-as-sociated proteins, particularly fimbrin and vil-lin. Calmodulin and a myosin-like ATPase connect the microfilaments laterally to the plasma membrane. Fodrin, another microfila-ment-associated protein, anchors the actin fibers to each other at the base, as well as attaching them to the cytoplasmic membrane and to a network of intermediate filaments. In this example, the microfilaments have a mainly static function. In other cases, actin is also involved in dynamic processes. These include muscle contraction (see p. 332), cell movement, phagocytosis by immune cells, the formation of microspikes and lamellipo-dia (cellular extensions), and the acrosomal process during the fusion of sperm with the egg cell. 

The diffraction data were also used to guide the selection of the best preserved e.m. images of decorated actin which were then used for a 3-D reconstruction (Amos et al., 1982). In this work, it was suggested that a myosin head interacts with two actin monomers (while still retaining a 1 1 stoichiometry), but this point has not been proved definitively. 

Dictyostelium discoideum (gene MHCK A, myosin II heavy chain kinase A, SwissProt-ID P42527 [25]) [25]... 

Cote, G.P. Bukiejko, U. Purification and characterization of a myosin heavy chain kinase from Dictyostelium discoideum. J. Biol. Chem., 262, 1065-1072 (1987)... 

A myosin head is made up of 850 residues, but the motor domain of a kinesin contains only -345. Like... 

Fig. 7. General structures of a number of different motors (A) myosin II interacting with actin, (B) kinesin carrying a cargo and interacting with a microtubule, and (C) cytoplasmic dynein, with its associated cargo-laden dynactin complex, interacting with a microtubule.

Fig. 16. (A) Myosin head SI showing the two domains referred to as the motor domain...

Coluccio, L. M., and Geeves, M. A. (1999). Transient kinetic analysis of the 130-kDa myosin I (MYR-1 gene product) from rat liver. A myosin I designed for maintenance of tension /. Biol. Chem. 274, 21575-21580. 

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