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Some thoughts by RSM about how this applies to Actin/Myosin

I agree that "but only if the particle is confronted by an appropriate potential for it to do work against" is essential. I agree that it is plausible that part of the work of the P is to unbind the ADP (as hinted in my abstract); I was regarding this as secondary, but as it is important to match the forces, I agree that it is better if the P has some standard potential to work against rather than just whatever the muscle is faced with.

A problem with your proposal is to explain how the binding of ATP does the external work. This is claimed by Oster to be true for the F1 motor (the part of ATPsynthase that can produce a torque by hydrolysis of ATP, though in "normal" operation it is driven in reverse by the F0 proton motor and synthesises ATP). Oster also proposes it is true of all ATPase motors (thus including myosin). But I cant see how it could fit with the believed cycle for myosin, since the binding of ATP results in no reported change in the conformation of the myosin ("hooked") (mind you, there are only two stages in the cycle for which structures have been determined, and even then with some uncertainties of interpretation because they have to use false versions of ATP to stop the cycle, eg with BeF3 instead of the terminal phosphate, so a lot is extrapolation). If your proposal is correct, it looks to me as if there would have to be:

either another power stroke, associated with the ATP binding, eg pulling in the tail of the myosin

or winding up of some internal "spring" which saves its energy and releases it as work during the standard power stroke (this is what several authors seem to favour, except they view the winding up of the spring as happening on hydrolysis; this could be plausible since it corresponds to the hooked to extended transition, except that in the extended state there is still and equilibrium with 10% unhydrolysed ATP but this may not be important).

It looks more likely to me that the ATP binding energy is used to detach the myosin from the actin (which must be a huge binding energy I imagine). Howard's basic cycle regards the ATP as bound before detachment occurs, but I think the two could be simultaneous (just as some authors think the P has to be released before the power stroke starts).

Thus perhaps it is the binding of myosin to actin that does the main work?!


Site last modified Tue Jul 5 12:32:01 BST 2005