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

Microtubule dynamics is regulated by various cellular proteins and perturbed by small-molecule compounds. To what extent the mechanism of the former resembles that of the latter is an open question. We report here structures of tubulin bound to the PN2-3 domain of CPAP, a protein controlling the length of the centrioles. We show that an alpha-helix of the PN2-3 N-terminal region binds and caps the longitudinal surface of the tubulin beta subunit. Moreover, a PN2-3 N-terminal stretch lies in a beta-tubulin site also targeted by fungal and bacterial peptide-like inhibitors of the vinca domain, sharing a very similar binding mode with these compounds. Therefore, our results identify several characteristic features of cellular partners that bind to this site and highlight a structural convergence of CPAP with small-molecule inhibitors of microtubule assembly.

Automated summary

The study demonstrates the binding of CPAP's PN2-3 domain with tubulin and the similarity in binding mode with fungal and bacterial inhibitors. This finding uncovers the characteristic features of cellular partners binding to this site and highlights the structural convergence of CPAP with small-molecule inhibitors.