Mechanisms of Processivity in Molecular Motors

Project: Research project

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Mechanisms of Processivity in Molecular Motors
Myosins and kinesins make up a diverse collection of molecular motors that generate force and movement
at the expense of nucleotide hydrolysis. Despite the fact that these two motor superfamilies share little
primary structure, members of each group often serve similar functions within the cell. For example, while
some myosins and kinesins transport vesicles, others generate the cortical tension required to maintain the
cytoskeleton and the mitotic apparatus. The central hypothesis of this project is that the physiologic
demands placed on a motor determine how ff behaves as an enzyme. It should therefore be possible to
predict key aspects of a motor's enzymology if its function within the cell is known. Myosin V and
conventional kinesin transport vesicles relatively long distances and work as single motors in isolation.
Consistent with the central hypothesis, these two motors share at least one feature of their enzymology--
both are processive. Processivity would be necessary for vesicle transporters that work in isolation, since
premature dissociation could have dire physiologic consequence. Thus, processivity serves as an example
of how a motor's enzymology can be shaped by its physiology. In this proposal, I will expand on this theme
of processivity as a response to physiologic demands. 1will use the data I have generated with kinesin to
formulate a model of how processivity works in molecular motors, and will test this model by comparing
kinesin to myosin V. In particular, I will examine three components of molecular motor enzymology whose
features should be predictable for vesicle transporters that work in isolation. These include the timing of the
forward step, the flexibility of the motor's mechanical element, and the mechanism of allosteric
communication. Taken together, these components are likely to determine how processive a motor is, and
like processivity itself, they too should be shaped by the demands of physiology. Determining how closely
these components conform to the predictions based on physiology will therefore provide a critical test of the
central hypothesis. Furthermore, if successful, this work will support the argument that understanding how a
motor works in vitro as an enzyme can provide valuable insights into how it works in vivo in the cell.
StatusNot started

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