Switching in Kinesin

Conformational Switching in Kinesin A. Comparison with Myosin 

Myosins are actin-based motors (see Chapter 5). The reason for considering myosin in the context of microtubule motors is that the catalytic domains of myosin and kinesin share structural similarities indicating that both families use a similar mechanism for energy conversion. The structural relationship between these families suggests that both descend from a common ancestor, a primordial nucleotide binding protein (Kull et ah, 1998). 

More than 18 classes of myosin have been identified in different organisms so far. Myosins of class V and class XI (the plant class V) are most akin to kinesin because they are dimeric, plus end (barbed end)-directed, processive motors used for membrane and particle transport along actin filaments. There is also a class of myosins with reversed motility (class VI). It is not yet clear whether these are monomeric or dimeric. Myosin-I, the first class of unconventional myosins to be identified, comprises monomeric motors with a basic tail that interacts by electrostatic interaction with the cargo. 

The structure of the myosin-II motor domain has been determined in various nucleotide states by crystal structure analysis using constructs originating from diverse sources (chicken skeletal and smooth muscle 

It has long been surmised that switch-2 movement and the concomitant swinging of the lever arm must be controlled by binding to and detachment from the actin filament to avoid futile consumption of ATP. However, direct evidence was lacking because near-atomic resolution crystal structures are necessarily obtained in the absence of the filament. Now, crystal structures of Dictyostelium myosin II (Reubold et at, 2003) and chicken myosin-V (Coureux et al., 2003) have revealed that the switch-1 motif can also exist in open and closed conformations. It has been inferred that switch-1 opening may be coupled to cleft closure and tight binding of the myosin head to the actin filament. This conclusion is supported by electron microscopy (Holmes et al., 2003) and fluorescence spectroscopy (Conibear et al., 2003) studies of the acto-myosin complex, which show that the concepts derived from crystal structures of isolated myosin heads are indeed valid for the functional complex. 

---