Muscle contraction model protein

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. 

Collagen fibrils seem ideally constructed to provide simple experimental models which may be used, by observation of swelling, contraction, and extension as functions of chemical or physical environments, to simulate the possible roles of protein fibrous systems in tissues or to learn how the environmental factors influence protein chain configuration in general. Pryor (181) has already offered suggestions of this sort in connection with problems of muscle contraction. 

The very most dramatic way to increase the oU-like nature of a model protein is the removal of an attached phosphate. This is demonstrated in Figure 2.12A. Calcium ion binding to a pair of carboxylates is second only to protonation of a carboxylate in driving hydrophobic association (See Figvnes 5.27 and 5.34). Tims, the combination of calcium ion binding to a pair of carboxylates followed by phosphate removal, as occurs in muscle contraction, provides perhaps the most potent means of bringing about hydrophobic association and the associated contraction. It is our view that hydropho-... 

Figure 2.15. A primitive swinging cross-bridge/ sliding filament model of muscle contraction is introduced for the purpose of providing a conceptual bridge from the simple oil-like dissociation/assoda-tion for the opening/closing of a clam-shaped globular protein toward the more complex structural aspects of muscle contraction. Major limitations in...

Hydrophobic Association in Muscle Contraction and in Contractile Model Proteins Phenomenological Correlations... 

The phenomena that drive muscle contraction—thermal activation, pH activation, calcium ion activation, stretch activation in insect flight muscle, and dephosphorylation itself—have all been shown to drive contraction by hydrophobic association in the elastic-contractile model proteins discussed in Chapter 5. As concerns a pair of hydrophobic domains, all of these processes surmount the T,-divide (the cusp of insolubility in Figure 7.1) to go from a soluble state to an insoluble state either by raising the... 

Phosphate attached to a model protein is three to four times more effective on a mole fraction basis than carboxylate in raising the T,-divide for hydrophobic association, which we have shown is due to a decrease in hydrophobic hydration (see Figures 5.25 and 5.27). Dephosphorylation, therefore, would re-establish hydrophobic hydration and dramatically lower the Trdivide, which is to lower the temperature range of the cusp of insolubility to below physiological temperature. The result would be an insolubilization of hydrophobic domains (a hydrophobic association) that we consider to be the power stroke of muscle contraction. 

Coherence of Phenomena Between Contraction of Muscle and Contraction of Model Proteins Using the Inverse Temperature Transition... 

As reviewed in Chapter 7 with a focus on the issue of insolubility, extensive phenomenological correlations exist between muscle contraction and contraction by model proteins capable of inverse temperature transitions of hydrophobic association. As we proceed to examination of muscle contraction at the molecular level, a brief restatement of those correlations follows with observations of rigor at the gross anatomical level and with related physiological phenomena at the myofibril level. Each of the phenomena, seen in the elastic-contractile model proteins as an integral part of the comprehensive hydrophobic effect, reappear in the properties and behavior of muscle. More complete descriptions with references are given in Chapter 7, sections 7.2.2, and 7.2.3. 

Raising the temperature to drive contraction by hydrophobic association is the fundamental property of the consilient mechanism as demonstrated in Chapter 5 by means of designed elastic-contractile model proteins. Thermal activation of muscle contraction also correlates with contraction by hydrophobic association, but assisted in this case by the thermal instability of phosphoanhydride bonds associated with ATP, which on breakdown most dramatically drive hydrophobic association. In particular, both muscle and cross-linked elastic protein-based polymer, (GVGVP) contract on raising... 

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. 

Although there are no positive Indications that structured water plays a role in the mechanism of muscle contraction, a theoretical mechanism employing the Ice lattice can be devised. Such a scheme uses protein-water interactions In two phases Involving Interchanging enol and keto forms of the peptide carbonyls, and was first mentioned as a possible contraction mechanism In an Informal discussion A coiq>lete elaboration of this concept as a model for muscle contraction has been publlshed. This model, which employs water In an active structural and mechanical sense, may be relevant to the earlier observation of Goodall that proton transfer could be the rate-determining step in muscle contraction. Home and Johnson have shown that variables such as pressure, ten erature, and Isotope (D2O) may Influence proton transfer In the aqueous environment, and each of these variables has been shown to have an effect on muscle contraction. 

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