Structural convergence for tubulin binding of CPAP and vinca domain microtubule inhibitors

Abstract

Significance Microtubules are dynamic assemblies of αβ-tubulin that are involved in key cellular functions, including cell division and intracellular transport. Microtubule dynamics is inhibited by several families of small molecules, some of which are used in oncology. The extent to which these compounds target the binding sites of cellular partners of tubulin remains poorly characterized. We show here that a region of the CPAP protein binds to the so-called vinca domain of β-tubulin in a way very similar to that of peptide-like inhibitors produced by bacteria and fungi. Therefore, our work identifies a structural convergence for tubulin binding between inhibitors and a regulator of microtubule dynamics.