The case for a common ancestor: kinesin and myosin motor proteins and G proteins

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 similariti es, the evolutionary relationships between these proteins, even among the m otor proteins, has not been obvious, since the topological connectivities o f the core overlapping structural elements in these transducing proteins ar e not identical to one another. Using secondary structure topology, compari son of functional domains and active site chemistry as criteria for related ness, we propose a set of rules for determining potential evolutionary rela tionships between proteins showing little or no sequence identity. These ru les 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 my osin show significant chemical conservations within and outside of the acti ve site, and present an evolutionary scheme that produces their respective topologies from a hypothetical ancestral protein. We also show that, when c ompared with various other P-loop-containing proteins, the cytoskeletal mot ors are most similar to G proteins with respect to topology and active site chemistry. We conclude that kinesin and myosin, and possibly G proteins, a re probably directly related via divergent evolution from a common core nuc leotide-binding motif, and describe the likely topology of this ancestor. T hese proteins use similar chemical and physical mechanisms to both sense th e 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. (C) Kluwer Academic Publ ishers.