The structured core of human β tubulin confers isotype-specific polymerization properties

Diversity in cytoskeleton organization and function may be achieved through variations in primary sequence of tubulin isotypes. Recently, isotype functional diversity has been linked to a tubulin code in which the C-terminal tail, a region of substantial sequence divergence between isotypes, specifies interactions with microtubule-associated proteins. However, it is not known whether residue changes in this region alter microtubule dynamic instability. Here, we examine recombinant tubulin with human beta isotype IIB and characterize polymerization dynamics. Microtubules with beta IIB have catastrophe frequencies approximately threefold lower than those with isotype beta III, a suppression similar to that achieved by regulatory proteins. Further, we generate chimeric beta tubulins with native tail sequences swapped between isotypes. These chimeras have catastrophe frequencies similar to that of the corresponding full-length construct with the same core sequence. Together, our data indicate that residue changes within the conserved beta tubulin core are largely responsible for the observed isotype-specific changes in dynamic instability parameters and tune tubulin's polymerization properties across a wide range.