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

Proc Natl Acad Sci U S A. 2022 May 10;119(19):e2120098119. doi: 10.1073/pnas.2120098119. Epub 2022 May 4.


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 α-helix of the PN2-3 N-terminal region binds and caps the longitudinal surface of the tubulin β subunit. Moreover, a PN2-3 N-terminal stretch lies in a β-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.

Keywords: centrioles; cytoskeleton; microtubule dynamics; peptide inhibitor; structural biology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Microtubules / metabolism
  • Protein Binding
  • Tubulin Modulators
  • Tubulin* / metabolism
  • Vinca* / metabolism


  • Tubulin
  • Tubulin Modulators