Substoichiometric Binding of Taxol Suppresses Microtubule Dynamics

We have measured the effects of taxol (10 nM to 1 microM) on the growing and shortening dynamics at the ends of individual bovine brain microtubules in vitro and have correlated the effects both with the stoichiometry of taxol binding to tubulin in microtubules and with the changes in the microtubule polymer mass. The results indicate that taxol suppresses microtubule dynamic instability differently depending upon the stoichiometry of taxol binding to the microtubules. At the lowest effective concentrations ( or = 1 microM taxol and > or = 0.1 mol of taxol bound/mol of tubulin in microtubules), microtubule mass increases sharply and dynamics is almost completely suppressed. The data support the hypothesis that binding of a molecule of taxol to a tubulin subunit in microtubules induces a conformational change in that subunit that strongly reduces its ability to dissociate when the subunit becomes exposed at the microtubule end.