New insights into the mechanism of force generation by kinesin-5 molecular motors.

Kinesin-5 motors are members of a superfamily of microtubule-dependent ATPases and are widely conserved among eukaryotes. Kinesin-5s typically form homotetramers with pairs of motor domains located at either end of a dumbbell-shaped molecule. This quaternary structure enables cross-linking and ATP-driven sliding of pairs of microtubules, although the exact molecular mechanism of this activity is still unclear. Kinesin-5 function has been characterized in greatest detail in cell division, although a number of interphase roles have also been defined. The kinesin-5 ATPase is tuned for slow microtubule sliding rather than cellular transport and-in vertebrates-can be inhibited specifically by allosteric small molecules currently in cancer clinical trials. The biophysical and structural basis of kinesin-5 mechanochemistry is being elucidated and has provided further insight into kinesin-5 activities. However, it is likely that the precise mechanism of these important motors has evolved according to functional context and regulation in individual organisms.