Structural convergence for tubulin binding of CPAP and vinca domain microtubule inhibitors - Structure et Activité des Biomolécules Normales et Pathologiques Access content directly
Journal Articles Proceedings of the National Academy of Sciences of the United States of America Year : 2022

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

Abstract

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 a-helix of the PN2-3 N-terminal region binds and caps the longitudinal surface of the tubulin b subunit. Moreover, a PN2-3 N-terminal stretch lies in a b-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 molecules inhibitors of microtubule assembly.
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Dates and versions

hal-03431978 , version 1 (17-11-2021)
hal-03431978 , version 2 (08-03-2022)

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Valérie Campanacci, Agathe Urvoas, Liza Ammar Khodja, Magali Aumont-Nicaise, Magali Noiray, et al.. Structural convergence for tubulin binding of CPAP and vinca domain microtubule inhibitors. Proceedings of the National Academy of Sciences of the United States of America, 2022, 119, pp.e2120098119. ⟨10.1073/pnas.2120098119⟩. ⟨hal-03431978v2⟩
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