Searching for kinesin's mechanical amplifier

Ronald D. Vale, Ryan Case, Elena Sablin, Cindy Hart, Robert Fletterick

Abstract

Kinesin, a microtubule–based motor, and myosin, an actin–based motor, share a similar core structure, indicating that they arose from a common ancestor. However, kinesin lacks the long lever–arm domain that is believed to drive the myosin power stroke. Here, we present evidence that a much smaller region of ca. 10–40 amino acids serves as a mechanical element for kinesin motor proteins. These ‘neck regions’ are class conserved and have distinct structures in plus–end and minus–end–directed kinesin motors. Mutagenesis studies also indicate that the neck regions are involved in coupling ATP hydrolysis and energy into directional motion along the microtubule. We suggest that the kinesin necks drive motion by undergoing a conformational change in which they detach and re–dock onto the catalytic core during the ATPase cycle. Thus, kinesin and myosin have evolved unique mechanical elements that amplify small, nucleotide–dependent conformational changes that occur in their similar catalytic cores.