Muscle contraction hydrophobic associations

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-... 

From the perspective of the consilient mechanism, the assembly of filaments as required for muscle contraction and the necessary movement of components within the cell involves hydrophobic association/dissociation between composite subunits. The actin thin filament of... 

In Chapter 8, more structural background and molecular details of contraction exhibited by the linear myosin II motor are considered after, in Chapter 5, the physical basis for the apolar (oil-like)-polar (vinegar-like) repulsive energy that controls hydrophobic association is experimentally and analytically developed. The crystal structures of the cross-bridge of scallop muscle provide remarkable examples of the consilient mechanism functioning in this protein-based machine ... 

Phosphorylation, the covalent attachment of a phosphate to an OH group, has been to date the most effective way to raise the temperature of the T,-divide. Thus, dephosphorylation, removal of phosphate, has been the most effective way to lower the temperature of the T,-divide and thereby the most effective way to drive hydrophobic association and its equivalent of contraction. This is similar to a primary event in muscle contraction (see Chapters 7 and 8). The shift in the T,-divide on binding of ATP can be as great as or greater than simple phosphorylation, depending on the interactions of ATP at the binding site. As discussed in Chapter 8, section 8.5, ATP binding drives hydrophobic dissociation, whereas loss of phosphate drives hydrophobic association both for the attachment to actin and for the power stroke to... 

Tliese examples of rigor at the gross anatomical level in muscle are manifestations of hydrophobic association at the molecular level they reflect the fundamental role of hydrophobic association/dissociation in the function of muscle. These occurrences of rigor in muscle do not support the view of electrostatic interactions, of direct charge-charge interactions independent of hydrophobic domains, being predominant in muscle function. These anatomical manifestations that correlate muscle contraction with hydrophobic association continue below the physiological level. 

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... 

Mammalian muscle acts as though it is poised for hydrophobic association at room temperature much as is the (GVGVP) elastic-contractile protein-based polymer on which are based the visually demonstrated contractions reviewed in Chapter 5. 

S Dephosphorylation Initiates Hydrophobic Associations of Muscle Contraction... 

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. 

Scenario of Muscle Contraction by the Inverse Temperature Transition of Hydrophobic Association... 

In our view, AG.p provides the basis whereby raising the free energy of ADP and P , by forced apposition of the very hydrophobic side of the y-rotor in ATP synthase, results in synthesis of ATP. Also, in myosin II motor AG,p provides the basis whereby this ATPase drives muscle contraction. In particular, in broad-brush strokes, ATP binds in a cleft directed in two directions, (1) toward the hydrophobic association of the cross-bridge to actin binding site and (2) toward the hydrophobic association between the head of the lever arm and the amino-terminal domain of the cross-bridge. Directing the ATP thirst for water in both... 

Contraction by the muscle myosin II motor is another example of hydrophobic association... 

Hypothesis Efficient Production of Motion by Muscle Contraction Derives from the Hydrophobic and Elastic Consilient Mechanisms, Whereby Dephosphorylation Results in Hydrophobic Association Coupled to Near-ideal Elastic Force Development... 

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... 

At the level of the myofibril, the addition of calcium ion, the lowering of pH, and stretching have each been shown to activate muscle contraction as well as to drive contraction of suitably designed elastic contractile protein-based polymers by hydrophobic association (see more extensive discussion in Chapter 7). 

In Figures 8.47 through 8.58, two states of the myosin II motor are compared using specific reference conditions. In our view, these two states differ most dramatically by their extents of hydrophobic association. Clearly, the state with less polar occupanQr of the nucleotide binding site favors greater hydrophobic association, and the state with more polar occupancy of the nucleotide binding site favors hydrophobic dissociation. The differences between the two states become explicable in terms of the hydrophobic and elastic consilient mechanisms, and the difference between the two states provides for displacement of the sort required for the motion of muscle contraction. 

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