CRYSTAL-STRUCTURE OF THE KINESIN MOTOR DOMAIN REVEALS A STRUCTURAL SIMILARITY TO MYOSIN

KINESIN is the founding member of a superfamily of microtubule-based m otor proteins that perform force-generating tasks such as organelle tr ansport and chromosome segregation(1,2). It has two identical similar to 960-amino-acid chains containing an amino-terminal globular motor d omain, a central alpha-helical region that enables dimer formation thr ough a coiled coil, and a carboxy-terminal tail domain that binds ligh t chains and possibly an organelle receptor(1). The kinesin motor doma in 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) a nd dynein (1,000 amino acids), and is the smallest known molecular mot or. Here, we report the crystal structure of the human kinesin motor d omain with bound ADP determined to 1.8-Angstrom resolution by X-ray cr ystallography. The motor consists primarily of a single alpha/beta arr owhead-shaped domain with dimensions of 70x45x45 Angstrom. Unexpectedl y, it has a striking structural similarity to the core of the catalyti c domain of the actin-based motor myosin. Although kinesin and myosin have virtually no amino-acid sequence identity, and exhibit distinct e nzymatic(4-6) and motile(7-10) properties, our results suggest that th ese two classes of mechanochemical enzymes evolved from a common ances tor and share a similar force-generating strategy.