Figure 3. A positive correlation between k_ON and k_OFF is consistent with an energy landscape model for diffusive binding.

(A) Association rates (k_ON) for MCAK(FL) and each of the three tested MCAK mutants plotted against the respective dissociation rates (k_OFF). This plot demonstrates a positive relationship between k_ON and k_OFF, which can be explained by a transitional barrier of variable height as shown in (B). The MCAK molecule (blue) must pass through the high-energy transitional state in order to switch between the two stable low energy states: free-in-solution or microtubule-bound. k_ON represents the transition from free-in-solution to microtubule-bound and is inversely dependent upon the height h₁. Alternately, k_OFF represents the transition from microtubule-bound to free-in-solution and is inversely dependent upon the height h₂. (C) The data indicates that MCAK(Mono) has a reduced barrier height in comparison to MCAK(FL), which explains the observed increases in both k_ON and k_OFF. (D) Conversely, MCAK(FL-NN) has an increased barrier height, indicated by the observed decreases in both k_ON and k_OFF. (E) Model illustrating the parameters that affect the flux of motors to the microtubule end and the removal of tubulin from the microtubule end.