The ATPase Cycle

FIGURE 2 (A) Myosin ATPase cycle. MT, MD, and MDP indicate myosin species with an ATP, ADP, and 

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Dynein, kinesin, and myosin are motor proteins with ATPase activity that convert the chemical bond energy released by ATP hydrolysis into mechanical work. Each motor molecule reacts cyclically with a polymerized cytoskeletal filament in this chemomechanical transduction process. The motor protein first binds to the filament and then undergoes a conformational change that produces an increment of movement, known as the power stroke. The motor protein then releases its hold on the filament before reattaching at a new site to begin another cycle. Events in the mechanical cycle are believed to depend on intermediate steps in the ATPase cycle. Cytoplasmic dynein and kinesin walk (albeit in opposite... 

In summary, therefore, solution and fiber biochemistry have provided some idea about how ATP is used by actomyosin to generate force. Currently, it seems most likely that phosphate release, and also an isomerization between two AM.ADP.Pj states, are closely linked to force generation in muscle. ATP binds rapidly to actomyosin (A.M.) and is subsequently rapidly hydrolyzed by myosin/actomyosin. There is also a rapid equilibrium between M. ADP.Pj and A.M.ADP.Pj (this can also be seen in fibers from mechanical measurements at low ionic strength). The rate limiting step in the ATPase cycle is therefore likely to be release of Pj from A.M.ADP.Pj, in fibers as well as in solution, and this supports the idea that phosphate release is associated with force generation in muscle. 

FIGURE 5-12 A processive clamp model for the ATPase cycle of the ABC transporter Mdllp. ATP binding (step I) on NBD domains of both monomers induces formation of the dimer (step 2). After ATP hydrolysis by the first NBD (step 3), either the P, is released first (step 4), followed by hydrolysis of the second ATP step 5) and release of the second P, step 8), or the second ATP is hydrolyzed first step 6) and then both phosphates are set free steps 7 and 8). After both ATPs are hydrolyzed to ADP and both phosphates are released, the dimeric complex dissociates step 9) and ADP step 10) is released. The hydrolysis cycle can then start again with ATP binding. (With permission from Fig. 7 of reference [34].)... 

The detailed mechanism by which ATP hydrolysis is coupled to transport awaits determination of the protein s three-dimensional structure, but a current model (Fig. 11-37) proposes that the ATPase cycles between two forms, a phosphorylated form (designated P-Enzn) with high affinity for K+ and low affinity for Na+, and a dephosphorylated form (Enz ) with high affinity for Na+... 

These proteins show differences in their cycles that have implications for their chaperone activities. We will use the available data to provide for these homologs a comparative description of the mechanistic features of the ATPase cycles, the substrate binding features, the coupling mechanism, and the regulation by co-chaperones. 

IV. Conformational Changes in Hsp90 Accompanying the ATPase Cycle. 166... 

Nishiyama M, Muto E, Inoue Y, Yanagida T, Higuchi H. 2001. Suhsteps within the 8-nm step of the ATPase cycle of single kinesin molecules. Nature Cell Biology 3 425. 

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