ATPase cycle

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].)... 

Repacking of the transmembrane domains of P-glycoprotein during the transport ATPase cycle. EMBO Journal, 20, 5615-5625. 

An overall scheme for Ca " -ATPase activity, based on structures of hve different states in the Ca " -ATPase cycle, has been proposed by Toyoshima et al. ... 

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+... 

Figure 5. Different modes of operation of the Na+-K+-pump that can be detected by addition of radioactive isotopes to sealed vesicular preparations of defined sidedness. The canonical flux mode is the ATP-driven exchange of three cytoplasmic Na+ for two extracellular K+. In Na+-Na+-exchange without net hydrolysis, only the Na+ limb of the Na+-K+-ATPase cycle is used. In the K+ K+-exchange mode, only the K+-limb of the Na+-K+-ATPase cycle is used. In ATP-driven Na+ Na+-exchange, the whole cycle is involved, but extracellular Na+ substitutes for K+ (m = 3, n = 2). In ATP-driven Na+-efflux, the whole cycle is involved, but the transport sites return empty from the extracellular to the cytoplasmic surface. Reproduced from Lauger, 1991 with permission from Sinauer Associates, Inc.

ATP-dependence of overall turnover. The behavior of the Ca2+-ATPase cycle is in accordance with a labile nature of the putative Eq form of Ca2+-ATPase, and contrary to the very stable K+-occluded form of Na+-K+-ATPase, the Ca2+-ATPase E2 form does not possess very low affinity for ATP. 

De Foresta, B Champeil, P., Le Maire, M. (1990). Different classes of tryptophan residues involved in the conformational changes characteristic of the sarcoplasmic reticulum Ca2+-ATPase cycle. Eur. J. Biochem. 194,383-388. 

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. 

---