Self-assembly myosin

Kuczmarsld, E.R. and Spudich, J.A. (1980). Regulation of myosin self-assembly phosphoiylation of Dictyostelium heavy chain inhibits thick filament formation. Proc. Natl. Acad. Sci. U.S.A. 77, 7292-7296. 

The interaction of actin and myosin is key to the generation of contractile forces in skeletal muscles. Skeletal muscles are composed of thick and thin filaments the thick filaments are composed primarily of myosin and thin filaments contain actin. The interaction between the two is a reversible self-assembly process that is followed by disassembly that separates actin from myosin. This separation initiates movement of myosin with respect to actin and results in shortening of the muscle, causing force generation. It is the assembly and disassembly process that we are interested in in this section. 

How does this cycle apply to muscle contraction Myosin molecules self-assemble into thick bipolar structures with the myosin heads protruding at both ends of a bare region in the center (Figure 34.19). Approximately 500 head domains line the surface of each thick filament. These domains are paired in myosin dimers, but the two heads within each dimer act independently. Actin filaments associate with each head-rich region, with the barbed ends of actin toward the Z-line. In the presence of normal levels of ATP, most of the myosin heads are detached from actin. Each head can independently hydrolyze ATP, bind to actin, release Pj, and undergo its power stroke. Because few other heads are... 

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. 

The muscle cell contains predominantly water, and the organisation of the self-assembled actin and myosin threads, which is based on hydrophobic interaction, must follow the general principles outlined in Chapter 4. In contrast to the simple liquid-crystalline systems considered there, we do not know the curvature of the interface. A description based on surfaces with constant average curv ature nonetheless appears the most reasonable line of attack, due to the analog with other self-assembled systems. 

To form the thick filaments, myosin molecules self-assemble into thick bipolar structures with the myosin heads protruding at both ends of a bare region in the center (Figure 34.14A). Approximately 500 head domains line the surface of each thick filament. Each head-rich region associates with two... 

Craig SW, Pollard TD (1982) Actin binding proteins. Trends Biochem Sci 7 8892 Cremo CR, Sellers JR, Facemyer KC (1995) Two heads are required for phosphorylation-dependent regulation of smooth muscle myosin. J Biol Chem 270 21712175 Cross RA, Geeves MA, Kendrick-Jones J (1991) A nucleationelongation mechanism for the self-assembly of side polar sheets of smooth muscle myosin. EMBO J 10 747756 Cross RA, Vandekerckhove J (1986) Solubility-determining domain of smooth muscle myosin rod. FEBS Lett 200 355360... 

Actin Collagen Fibre Fracture Hydrophobic bond Myosin Nature Self-assembly Silk Smart composite Structural hierarchy Toughness... 

The myosin protomers can self-associate to form a thick filament by the assembly of some 400 myosin tails in a staggered side-by-side packing with the myosin heads projecting at regular intervals in a helical array (Fig. 5-32). The thick filament is bipolar with a 150 nm bare zone in the center where two oppositely oriented sets of myosin tails come together. The center of this region is called the M line. This thick filament forms part of a myofibril. 

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