A biochemical mechanism for Stu2/XMAP215-family microtubule polymerases

A recent study has unveiled a quantitative biochemical mechanism governing the Stu2/XMAP215-family microtubule polymerases. These polymerases utilize tubulin-binding TOG domains to catalyze microtubule growth, although the link between polymerase activity and the number of TOGs remains unclear. Researchers tested if an enzyme-like biochemical model for the actin polymerase Ena/VASP could be applied to quantify the relationship between Stu2 microtubule polymerase activity and the number of its TOGs, as well as the rate constants governing their interactions with tubulin.

The study found that Stu2 activity demonstrated enzyme-like characteristics consistent with the biochemical model. Stu2 stimulated microtubule growth rates with a hyperbolic dependence on tubulin concentration, while the amount of Stu2 on the microtubule end remained constant regardless of tubulin concentration. Complementary measurements of TOG:tubulin binding revealed a high affinity of 10 nM and a slow dissociation rate of 0.03 s⁻¹.

These polymerase and binding measurements can be unified within the biochemical model, suggesting that Stu2 functions as a tubulin-shuttling antenna on the microtubule end, primarily limited by the rate of tubulin:TOG association.

This research provides a quantitative biochemical mechanism for TOG-based polymerases. Moreover, the fact that unrelated microtubule and actin polymerases utilize the same enzyme-like mechanism underscores an instance of convergent evolution within the cytoskeleton.