Identification of Key Structural Elements of ATP-Dependent Molecular Motors

Molecular motors perform diverse functions in cells, ranging from muscle contraction, cell division, DNA/RNA replication, protein degradation, and vesicle transport. The majority of molecular motors use energy from the ATP hydrolysis cycle, converting chemical energy into mechanical work in cells. All ATP-dependent molecular motors have a similar ATP binding site, although the functions can be drastically different. Myosins comprise a large group of ATP-dependent molecule motors. The structure-function relationship governing different functions for different myosin families remains elusive. Hypothesizing that members of each family possess conserved residues for their consensus functions and residues distinctive from those of other families to differentiate their functions from functions of other myosin families, we developed an algorithm for comparative sequence analysis in a phylogenic hierarchy to identify family-specific residues for 38 myosin families/subfamilies that comprise human myosin members. We found a number of family-specific residues that have been reported, such as residues in β-cardiac myosin associated with hypertrophic cardiomyopathy and residues in myosin 7A ass