Hydrophobic dissociation consilient mechanism

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... 

Relationship of the Consilient Mechanism to Cold Denaturation and to Hydrophobic Dissociation on Being Made More Polar... 

Hydrophobic association on raising the temperature is the most fundamental aspect of the consilient mechanism, arising as it does from the inverse temperature transition. An equivalent statement would be that hydrophobic dissociation on lowering the temperature is fundamental to the consilient mechanism. Historically, this has been called cold denaturation of enzymes. In our view, those protein systems that associate on heating to physiological temperatures in order to achieve a functional state should be considered in terms of the consilient mechanism. 

The consilient mechanism was bom out of controlling the hydrophobic association-dissociation of elastic-contractile model proteins to achieve the possibility of some 18 classes of pairwise energy conversions (see Chapter 5, section 5.6). In the process a set of five Axioms became the phenomenology out of which the consilient mechanism arose. For the first time a common groundwork of explanation was able to perform the diverse energy conversions of biology. 

Applying what is now the consilient mechanism for hydrophobic association to the elastic fiber, the prediction became that oxidation of the elastic fiber by a natural enzyme with the biological role of producing superoxide and hydrogen peroxide would cause hydrophobic dissociation evidenced by a swelling and a loss of elastic recoil. A xanthine oxidase superoxide... 

By the hydrophobic consilient mechanism for the myosin II motor and specifically by means of AG p, ATP binding effects both hydrophobic dissociation from the actin binding site and release of the hydrophobic association at the head of the lever arm, allowing the cross-bridge to move forward toward the next attachment site. Of course, loss of phosphate would reconstitute the hydrophobic associations, that is, would effect hydrophobic re-attachment to the actin binding site in concert with re-association of the head of the lever arm with the amino-termincil domain to result in the powerstroke. Section 8.5.4 presents crystal structure stereo views from which the above-noted perspective derives. 

Release of the y-phosphate from protein-bound ATP, leaving bound ADP, restores much hydrophobic association that existed in the protein before ATP binding. Release of the y-phosphate permits reconstitution of sufficient hydrophobic hydration to drive hydrophobic association. In the broad view of the consilient mechanism, as regards ATPases, ATP binding causes hydrophobic dissociation, and P and ADP release re-establishes maximal hydro-phobic association. In terms of the movable cusp of insolubility, binding of the polar ATP molecule raises the temperature of the movable cusp of insolubility to give solubility, and the decrease in polaritys on phosphate release lowers the movable cusp of insolubility to re-establish the insolubility of hydrophobic association... 

The focus has been on both aspects of the consilient mechanism (hydrophobic association/ dissociation and elastic force development/ relaxation) involved in the unique domain movement for electron transfer within Complex III. In what follows, the same aspect of hydrophobic association/dissociation of the consilient mechanism is proposed for facilitating proton gating. 

Our conclusion is that dissociation of the RIP from the Q site in a single step represents a unique intersection of electron transfer and proton translocation that simultaneously employs both the hydrophobic and elastic consilient mechanisms. 

In the context of relevance of the consilient mechanism to function of the myosin II motor, remarkable points are the location and orientation of ATP molecules bound to the crossbridge and access to control hydrophobic associations/dissociations. As considered below in section S.5.4.2, narrow clefts function as conduit through which forces arising from the polar phosphates are directed at a target site. 

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. 

Expectation 2 That the ADP plus Pi state at the cross-bridge active site effects a repulsive AGap force for dissociation of hydrophobic domains within the cross-bridge. Relevance of the hydrophobic consilient mechanism to the motion of contraction requires that formation of the most polar state, ADP " Mg + HPO/", effects hydrophobic dissociation within the cross-bridge. This sets the stage for the loss of Pi, that is, of HPO/", that drives the hydrophobic association required by the hydrophobic consilient mechanism as... 

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