A TOG:??-tubulin complex structure reveals conformation-based mechanisms for a microtubule polymerase.

ABSTRACT: Stu2p/XMAP215/Dis1 family proteins are evolutionarily conserved regulatory factors that use ??-tubulin-interacting tumor overexpressed gene (TOG) domains to catalyze fast microtubule growth. Catalysis requires that these polymerases discriminate between unpolymerized and polymerized forms of ??-tubulin, but the mechanism by which they do so has remained unclear. Here, we report the structure of the TOG1 domain from Stu2p bound to yeast ??-tubulin. TOG1 binds ??-tubulin in a way that excludes equivalent binding of a second TOG domain. Furthermore, TOG1 preferentially binds a curved conformation of ??-tubulin that cannot be incorporated into microtubules, contacting ?- and ?-tubulin surfaces that do not participate in microtubule assembly. Conformation-selective interactions with ??-tubulin explain how TOG-containing polymerases discriminate between unpolymerized and polymerized forms of ??-tubulin and how they selectively recognize the growing end of the microtubule.

SUBMITTER: Ayaz P 

PROVIDER: S-EPMC3734851 | biostudies-literature | 2012 Aug

REPOSITORIES: biostudies-literature