A METAL SWITCH FOR CONTROLLING THE ACTIVITY OF MOLECULAR MOTOR PROTEINS

Kinesins are molecular motors that require a divalent metal ion (e.g., Mg(2+)) to convert the energy of ATP hydrolysis into directed force production along microtubules. Here we present the crystal structure of a recombinant kinesin motor domain bound to Mn(2+) and ADP, and report on a serine to cysteine substitution in the switch 1 motif of kinesin that allows its ATP hydrolysis activity to be controlled by adjusting the ratio of Mn(2+) to Mg(2+). This mutant kinesin binds ATP similarly in the presence of either metal ion, but its ATP hydrolysis activity is greatly diminished in the presence of Mg(2+). In several different members of the kinesin superfamily, this defect is rescued by Mn(2+), providing a way to control both the enzymatic activity and force generating ability of these nanomachines.