Abstract
A structure-based model of myosin motor is built in the same spirit of our early work for kinesin-1 and Ncd towards physical understanding of its mechanochemical cycle. We find a structural adaptation of the motor head domain in post-powerstroke state that signals faster ADP release from it compared to the same from the motor head in the pre-powerstroke state. For dimeric myosin, an additional forward strain on the trailing head, originating from the postponed powerstroke state of the leading head in the waiting state of myosin, further increases the rate of ADP release. This coordination between the two heads is the essence of the processivity of the cycle. Our model provides a structural description of the powerstroke step of the cycle as an allosteric transition of the converter domain in response to the Pi release. Additionally, the variation in structural elements peripheral to catalytic motor domain is the deciding factor behind diverse directionalities of myosin motors (myosin V & VI). Finally, we observe that there are general rules for functional molecular motors across the different families. Allosteric structural adaptation of the catalytic motor head in different nucleotide states is crucial for mechanochemistry. Strain-mediated coordination between motor heads is essential for processivity and the variation of peripheral structural elements is essential for their diverse functionalities.
Highlights
Motors belonging to myosin superfamily are associated with a host of important cellular functions, including muscle contraction, cytokinesis, chemotaxis, targeted vesicle and organelle transport [1,2,3,4]
We find that a structural adaptation of the motor head domain in post-powerstroke state signals faster ADP release from the trailing head to maintain its processivity while directionality arises from a careful design of peripheral structural elements
In the step (iii ! iv), the ADP release should be faster in this conformation to allow for a faster access for the ATP to bind the head which is important for the speeding up of the cycle
Summary
Motors belonging to myosin superfamily are associated with a host of important cellular functions, including muscle contraction, cytokinesis, chemotaxis, targeted vesicle and organelle transport [1,2,3,4]. These motors perform mechanical work by producing movement on the actin filament powered by ATP hydrolysis [5,6,7]. Despite significant successes by these theoretical and experimental studies, there is still a need for a detailed structure-based comprehensive understanding of the unidirectional movement of these motors and the allosteric coordination between the heads for the processivity
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