Abstract
Recent studies have shown surprising structural and functional similarities between the motor domains of kinesin and myosin. Common features have also been described for motor proteins and G proteins. Despite these similarities, the evolutionary relationships between these proteins, even among the motor proteins, has not been obvious, since the topological connectivities of the core overlapping structural elements in these transducing proteins are not identical to one another. Using secondary structure topology, comparison of functional domains and active site chemistry as criteria for relatedness, we propose a set of rules for determining potential evolutionary relationships between proteins showing little or no sequence identity. These rules were used to explore the evolutionary relationship between kinesin and myosin, as well as between motor proteins and other phosphate-loop (P-loop) containing nucleotide- binding proteins. We demonstrate that kinesin and myosin show significant chemical conservations within and outside of the active site, and present an evolutionary scheme that produces their respective topologies from a hypothetical ancestral protein. We also show that, when compared with various other P-loop-containing proteins, the cytoskeletal motors are most similar to G proteins with respect to topology and active site chemistry. We conclude that kinesin and myosin, and possibly G proteins, are probably directly related via divergent evolution from a common core nucleotide-binding motif, and describe the likely topology of this ancestor. These proteins use similar chemical and physical mechanisms to both sense the state of the nucleotide bound in the active site, and then transmit these changes to protein partners. The different topologies can be accounted for by unique genetic insertions that add to the edge of a progenitor protein structure and do not disrupt the hydrophobic core.
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Kull, F.J., Vale, R.D. & Fletterick, R.J. The case for a common ancestor: kinesin and myosin motor proteins and G proteins. J Muscle Res Cell Motil 19, 877–886 (1998). https://doi.org/10.1023/A:1005489907021
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DOI: https://doi.org/10.1023/A:1005489907021