PT  - JOURNAL ARTICLE
AU  - Valérie Campanacci
AU  - Agathe Urvoas
AU  - Liza Ammar Khodja
AU  - Magali Aumont-Nicaise
AU  - Magali Noiray
AU  - Sylvie Lachkar
AU  - Patrick A. Curmi
AU  - Philippe Minard
AU  - Benoît Gigant
TI  - Structural convergence for tubulin binding of CPAP and vinca domain microtubule inhibitors
AID  - 10.1101/2021.10.19.464980
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2021.10.19.464980
4099  - http://biorxiv.org/content/early/2022/02/28/2021.10.19.464980.short
4100  - http://biorxiv.org/content/early/2022/02/28/2021.10.19.464980.full
AB  - 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.Competing Interest StatementThe authors have declared no competing interest.