Bi-pedaling motors move predominantly by hand-over-hand, i.e. while the leading head remains attached to its track the lagging head detaches from its rear position, advances alongside the attached head, and becomes the new leading head following filament rebinding.


A motors ability to walk hand-over-hand and to retain motility under heavy load, i.e. to move processively, require that at any given moment at least one of the heads stays tightly bound to the filament, or put differently, that each of the head remains attached at least 50% of the motors chemomechanical cycle. 

The stepping mechanisms for myosin V and VI provide good examples for how processivity can be achieved  by way of inter-head communication and chemomechanical coordination.



Myosin Stepping.jpg

1. The powerstroke by the leading head pulls the lagging head forward. Resistance from the tightly bound lagging head and from load of bound cargo create an opposite force that pulls the leading head backward. 

The backward strain activates two alternative mechanisms, both of which prevent binding of ATP and premature detachment of the leading head. In myosin V, strain-activated reduction in ADP release leads to slower entry of ATP, whereas in myosin VI, ADP is released at normal rate but binding of ATP is structurally inhibited.


2. Forward strain on the lagging head accelerates binding of ATP prompting head-filament dissociation.  

3. The now unrestrained lagging head swings past the leading head and advances towards its next binding site.

4. Filament re-association of the new leading head caps the step-generating events. The 72 nanometer leap  has resulted in a 36 nanometer center-of-mass displacement.