Myosin actin complex, structure

To date, three primary conformations of the myosin crossbridge that can be associated with states in the Lymn-Taylor cycle have been identified. These have been named the post-rigor structure (Fig. 2 and state 2 in Fig. 1), the pre-powerstroke structure (corresponding to the myosin products complex, M.D.P , state 3 in Fig. 1), and the rigor Iihe (or rigor structure if it is associated with actin) state (shown as state 1 in Fig. 1). A comparison of these structures leads to the identification the following important conformationally flexible elements ... 

The description of structure in complex chemical systems necessarily involves a hierarchical approach we first analyse microstructure (at the atomic level), then mesostructure (the molecular level) and so on. This approach is essential in many biological systems, since self-assembly in the formation of biological structures often takes place at many levels. This phenomenon is particularly pronounced in the complex structures formed by amphiphilic proteins that spontaneously associate in water. For example myosin molecules associate into thick threads in an aqueous solution. Actin can be transformed in a similar way from a monomeric molecular solution into helical double strands by adjusting the pH and ionic strength of the aqueous medium. The superstructure in muscle represents a higher level of organisation of such threads into an arrangement of infinite two-dimensional periodicity. 

Rayment, 1., et al. Structure of the actin-myosin complex and its implications for muscle contraction. Science 261 58-65, 1996. 

Rayment, L, Holden, H.M., Whittaker, M., Yohn, C.B., Lorenz, M., Holmes, K.C., Milligan, R.A. (1993b). Structure of the actin-myosin complex and its implications for muscle contraction. Science 261, 58-65. 

In addition to its effects on enzymes and ion transport, Ca /calmodulin regulates the activity of many structural elements in cells. These include the actin-myosin complex of smooth muscle, which is under (3-adrenergic control, and various microfilament-medi-ated processes in noncontractile cells, including cell motility, cell conformation changes, mitosis, granule release, and endocytosis. 

In striated muscle, there are two other proteins that are minor in terms of their mass but important in terms of their function. Tropomyosin is a fibrous molecule that consists of two chains, alpha and beta, that attach to F-actin in the groove between its filaments (Figure 49-3). Tropomyosin is present in all muscular and muscle-fike structures. The troponin complex is unique to striated muscle and consists of three polypeptides. Troponin T (TpT) binds to tropomyosin as well as to the other two troponin components. Troponin I (Tpl) inhibits the F-actin-myosin interaction and also binds to the other components of troponin. Troponin C (TpC) is a calcium-binding polypeptide that is structurally and functionally analogous to calmodulin, an important calcium-binding protein widely distributed in nature. Four molecules of calcium ion are bound per molecule of troponin C or calmodulin, and both molecules have a molecular mass of 17 kDa. 

Tropomyosin and troponin are proteins located in the thin filaments, and together with Ca2+, they regulate the interaction of actin and myosin (Fig. 43-3) [5]. Tropomyosin is an a-helical protein consisting of two polypeptide chains its structure is similar to that of the rod portion of myosin. Troponin is a complex of three proteins. If the tropomyosin-troponin complex is present, actin cannot stimulate the ATPase activity of myosin unless the concentration of free Ca2+ increases substantially, while a system consisting solely of purified actin and myosin does not exhibit any Ca2+ dependence. Thus, the actin-myosin interaction is controlled by Ca2+ in the presence of the regulatory troponin-tropomyosin complex [6]. 

If the cross-links or polymers are severed, then some elastic energy is released and the system will adopt a new (larger) equilibrium volume where greater distortion is conferred upon a meshwork that has fewer cross-links. Thus, upon increases in Ca2+, gelsolin activity leads to an increase in the volume of the actin-filament network. The additional influence of myosin on such a meshwork is similar to that proposed in the Stossel model. Thus, three-dimensional Ca2+ gradients (between a localised region of the cell surface and an external structure) can result in complex shape changes. 

The work that follows pertains primarily to actin networks. Many proteins within a cell are known to associate with actin. Among these are molecules which can initiate or terminate polymerization, intercalate with and cut chains, crosslink or bundle filaments, or induce network contraction (i.e., myosin) (A,11,12). The central concern of this paper is an exploration of the way that such molecular species interact to form complex networks. Ultimately we wish to elucidate the biophysical linkages between molecular properties and cellular function (like locomotion and shape differentiation) in which cytoskeletal structures are essential attributes. Here, however, we examine the iri vitro formation of cytoplasmic gels, with an emphasis on delineating quantitative assays for network constituents. Specific attention is given to gel volume assays, determinations of gelation times, and elasticity measurements. 

N ow that some of the major types of protein structures have been described it is appropriate to turn to the question of how protein structure relates to protein function. To explore this question, two protein systems, hemoglobin and the actin-myosin complex, are examined in detail. 

M. Lorenz, K. C. Holmes, and R. A. Milligan, Structure of the Actin-Myosin Complex and Its Implications for Muscle Contraction. Science 261 58-65, 1993. 

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.

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