Fig 1. Functional cycle of single- and double-headed myosin.
(A) Sequence of events of the mechanochemical cycle of the single-headed myosin. ATP bound (red) head (i) binds to the actin filament followed by the hydrolysis of ATP. The arm (black line on head) of this actin bound head (ii) in ADP + Pi state (pink) has a pre-powerstroke conformation. Phosphate (Pi) release induces the powerstroke conformational change to the lever arm (iii). Next, ADP (blue) is released from the bound head while keeping the post-powerstroke lever arm conformation (iv). Finally, the empty head (gray) detaches from the actin followed by an ATP intake. The ATP dependent unbound head experiences a repriming event to its stable pre-powerstroke lever arm conformation (v). Note that, state (v) is exactly same as state (i) with an additional stepping towards left and also the nucleotide dependent actin binding affinity information in the middle. (B) The sequence of events of the functional cycle of the double-headed myosin. In state (i), head 1 is in an ATP bound state and head 2 is bound to actin in an ADP state. ATP hydrolysis and subsequent binding to actin by head 1 provide a two-head bound myosin (ii). Head 1 releases phosphate (Pi) to transform into state (iii). In contrary to a single-head myosin, here, after Pi release, head 1 cannot perform powerstroke while head 2 is still bound. The green line shows the expected lever arm conformation of head 1. It is important to note here that the two-head-bound state iii could adopt an alternative conformation with the converters of both heads in a post-powerstroke conformation while the lever arm of the leading/trailing head bends backward/forward. Next, ADP releases from head 2 (iv) and subsequently ATP binds to the empty head. Head 2 now detaches from the actin and head 1 now performs its postponed powerstroke step. Finally, head 2 also perform its spontaneous repriming event to form state (v). Note that, state (v) is exactly same as state (i) with an additional stepping towards the left.