Principal Investigator Frank Solomon
The alpha-tubulin mutant tub1-724 is one of several mutations that arrest at low temperature with no microtubules. Since microtubule assembly itself is cold-sensitive, such mutations could affect the assembly reaction. However, the tub1-724 mutation destabilizes the heterodimer itself. This mutant beta-tubulin binds to beta-tubulin with lower affinity than does wild type beta-tubulin, and so enhances dissociation of the heterodimer to produce toxic free beta-tubulin. The amino acid changed in Tub1-724p is predicted to contact the GTP bound at the interface between a- and beta-tubulin in the heterodimer. The properties of this mutant constitute the first structure-function analysis of the heterodimer itself, and provide a tool for studying the mechanisms by which cells manage tubulin polypeptides. This mutant is also suppressed by a mutation in a ribosomal protein. This mutation has numerous microtubule phenotypes, providing another link between microtubule morphogenesis and expression.