Should the tubulins be members of the GTPase superfamily?

Abstract

The beta-subunit of the alpha/beta tubulin heterodimer resembles other members of the GTPase superfamily in that: it binds GTP, the GTP is hydrolysed to GDP on microtubule assembly and this induces a conformational change; it exhibits a similar nucleotide stereospecificity; aluminium and beryllium fluorides inhibit this hydrolysis-dependent conformational change; and beta-tubulin contains peptides which are similar to the consensus motifs characteristic of the GTPase superfamily proteins. By contrast, UV photo-cross-linking and other binding studies have identified peptides which may contribute to the GTP-binding site but which are absent from the GTPase superfamily proteins. We suggest that beta-tubulin has a 'dual personality', with the characteristics of the GTP-binding site depending upon the precise conformation of the protein and upon whether the experimental assays probe nucleotide binding or the hydrolytic mechanism. We suggest that the hydrolytic mechanism of beta-tubulin resembles that of the other members of the GTPase superfamily, although the differences within the consensus motifs dictate that the architecture of the GTP pocket cannot be identical.