Abstract
ATP synthases are unusually complex molecules, which fractionate most readily into two major units, one a water soluble unit called F1 and the other a detergent soluble unit called F0. In almost all known species the F1 unit consists of 5 subunit types in the stoichiometric ratio α3β3γδε while the F0 unit contains 3 subunit types (a, b, and c) in E. coli, and at least 10 subunit types (a, b, c, and others) in higher animals. It is now believed by many investigators that during the synthesis of ATP, protons derived from an electrochemical gradient generated by an electron transport chain are directed through the F0 unit in such a way as to drive the rotation of the single γ subunit, which extends from an oligomeric ring of at least 10 c subunits in F0 through the center of F1. It is further believed by many that the rotating γ subunit, by interacting sequentially with the 3 αβ pairs of F1 (360° cycle) in the presence of ADP, Pi, and Mg++, brings about via “power strokes” conformational/binding changes in these subunits that promote the synthesis of ATP and its release on each αβ pair. In support of these views, studies in several laboratories either suggest or demonstrate that F0 consists in part of a proton gradient driven motor while F1 consists of an ATP hydrolysis driven motor, and that the γ subunit does rotate during F1 function. Therefore, current implications are that during ATP synthesis the former motor drives the latter in reverse via the γ subunit. This would suggest that the process of understanding the mechanism of ATP synthases can be subdivided into three major levels, which include elucidating those chemical and/or biophysical events involved in (1) inducing rotation of the γ subunit, (2) coupling rotation of this subunit to conformational/binding changes in each of the 3 αβ pairs, and (3) forming ATP and water (from ADP, Pi, and Mg++) and then releasing these products from each of the 3 catalytic sites. Significantly, it is at the final level of mechanism where the bond breaking/making events of ATP synthesis occur in the transition state, with the former two levels of mechanism setting the stage for this critical payoff event. Nevertheless, in order to get a better grip in this new century on how ATP synthases make ATP and then release it, we must take on the difficult challenge of elucidating each of the three levels of mechanism.
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Pedersen, P.L., Ko, Y.H. & Hong, S. ATP Synthases in the Year 2000: Defining the Different Levels of Mechanism and Getting a Grip on Each. J Bioenerg Biomembr 32, 423–432 (2000). https://doi.org/10.1023/A:1005652605340
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DOI: https://doi.org/10.1023/A:1005652605340