Op18/stathmin caps a kinked protofilament-like tubulin tetramer

Oncoprotein 18/stathmin (Op18), a regulator of microtubule dynamics, was re combinantly expressed and its structure and function analysed. We report th at Op18 by itself can fold into a flexible and extended a-helix, which is i n equilibrium with a less ordered structure. In complex with tubulin, howev er, all except the last seven C-terminal residues of Op18 are tightly bound to tubulin. Digital image analysis of Op18:tubulin electron micrographs re vealed that the complex consists of two longitudinally aligned alpha/beta-t ubulin heterodimers. The appearance of the complex was that of a kinked pro tofilament-like structure with a flat and a ribbed side. Deletion mapping o f Op18 further demonstrated that (i) the function of the N-terminal part of the molecule is to 'cap' tubulin subunits to ensure the specificity of the complex and (ii) the complete C-terminal a-helical domain of Op18 is neces sary and sufficient for stable Op18:tubulin complex formation. Together, ou r results suggest that besides sequestering tubulin, the structural feature s of Op18 enable the protein specifically to recognize microtubule ends to trigger catastrophes.