CRYSTAL STRUCTURE OF THE KINESIN MOTOR DOMAIN REVEALS A STRCTURAL SIMILARITY TO MYOSIN F. Jon Kull, Elena P. Sablin, Rebecca Lau, Robert J. Fletterick, Ronald Vale, Department of Biochemistry and Biophysics, UCSF, San Francisco, CA 94143

Kinesin is the founding member of a large superfamily of microtubule-based motor proteins that perform force-generating tasks such as organelle transport and chromosome segregation. In this study, the crystal structure of the human kinesin motor domain with bound Mg-ADP was determined to 1.8 Å resolution by X-ray crystallography using two MIR derivatives, EMTS and 2'-iodo-ATP. Crystals grow in the orthorhombic space group P2₁2₁2₁ with one monomer per unit cell (48.5 x 67.9 x 113.0 Å). The motor consists primarily of a single a/ß arrowhead-shaped domain with dimensions of 70 x 45 x 45 Å. Unexpectedly, this motor exhibits a striking 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 and motile properties, our results suggest these two classes of mechanochemical enzymes evolved from a common ancestor and share a similar force-generating strategy.