Crystal structure of the kinesin motor domain reveals a structural similarity to myosin

KINESIN is the founding member of a superfamily of microtubule-based motor proteins that perform force-generating tasks such as organelle transport and chromosome segregation(1,2). It has two identical similar to 960-amino-acid chains containing an amino-terminal globular motor domain, a central alpha-helical region that enables dimer formation through a coiled coil, and a carboxy-terminal tail domain that binds light chains and possibly an organelle receptor(1). The kinesin motor domain of similar to 340 amino acids, which can produce movement in vitro(3), is much smaller than that of myosin (similar to 850 amino acids) and dynein (1,000 amino acids), and is the smallest known molecular motor. Here, we report the crystal structure of the human kinesin motor domain with bound ADP determined to 1.8-Angstrom resolution by X-ray crystallography. The motor consists primarily of a single alpha/beta arrowhead-shaped domain with dimensions of 70x45x45 Angstrom. Unexpectedly, it has a striking structural similarity to the core of the catalytic domain of the actin-based motor myosin. Although kinesin and myosin have virtually no amino-acid sequence identity, and exhibit distinct enzymatic(4-6) and motile(7-10) properties, our results suggest that these two classes of mechanochemical enzymes evolved from a common ancestor and share a similar force-generating strategy.