Model protein studies contraction

Hydrophobic association within a protein chain constitutes an element of contraction. From our design and study of elastic-contractile model proteins, a contraction comprises two distinct but interlinked physical processes. They are... 

Studies on muscle contraction carried out between 1930 and 1960 heralded the modem era of research on cytoskeletal stmctures. Actin and myosin were identified as the major contractile proteins of muscle, and detailed electron microscopic studies on sarcomeres by H.E. Huxley and associates in the 1950s produced the concept of the sliding filament model, which remains the keystone to an understanding of the molecular mechanisms responsible for cytoskeletal motility. 

Key findings that demonstrated that the 0 subunit is the essential component of L-type channels have come from studies of the channel activity of the expressed protein. Expression studies performed in mammalian liver fibroblasts have demonstrated that the oti subunit alone can form a channel [77] and contains the receptors for the DHPs, PAAs and diltiazem [64]. In very elegant studies using a mouse model of muscular dysgenesis it has been demonstrated that the ] subunit DNA can restore Ca currents and the charge movement that arises from the voltagesensing function of the channels to the mutant cells that normally lack these activities [21,78,79]. The restoration of these activities restores excitation-contraction coupling. Thus it is clear that the aj subunit is the major functional unit of L-type Ca channels. 

Most cell lines have lost some or many of the functions characteristic of the differentiated cells from which they were derived. Such relatively undifferentiated cells are poor models for investigating the normal functions of specific cell types. Better in this regard are several more-differentiated cell lines that exhibit many properties of normal nontransformed cells. These lines Include the liver tumor (hepatoma) HepG2 line, which synthesizes most of the serum proteins made by normal liver cells (hepatocytes). Another example consists of cells from a certain cultured fibroblast line, which under certain experimental conditions behave as muscle precursor cells, or myoblasts. These cells can be Induced to fuse to form myotubes, which resemble differentiated multlnucleated muscle cells and synthesize many of the specialized proteins associated with contraction. The results of studies with this cell line have provided valuable information about the differentiation of muscle (Chapter 22). Finally, as discussed previously, the MDCK cell line retains many properties of highly differentiated epithelial cells and forms well-defined epithelial sheets in culture (see Figure 6-6). 

The study of the interaction between two complementary macromolecules and the aggregation of the resulting complexes to a supermolecular structure in solution is of special interest, because many biological phenomena such as enzymatic processes, supermolecular assemblies in virus shells, and muscle contraction depend on specific protein-protein interactions. Studies on synthetic macromolecules may serve as models of such phenomena. 

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