Structural model for differential cap maturation at growing microtubule ends

• Main Authors: Juan Estévez-Gallego, Fernando Josa-Prado, Siou Ku, Ruben M Buey, Francisco A Balaguer, Andrea E Prota, Daniel Lucena-Agell, Christina Kamma-Lorger, Toshiki Yagi, Hiroyuki Iwamoto, Laurence Duchesne, Isabel Barasoain, Michel O Steinmetz, Denis Chrétien, Shinji Kamimura, J Fernando Díaz, Maria A Oliva
• Format: Article
• Language: English
• Published: eLife Sciences Publications Ltd 2020-03-01
• Series: eLife
• Subjects: microtubule; GTP-cap; dynamic instability; taxol
• Online Access: https://elifesciences.org/articles/50155

Microtubules (MTs) are hollow cylinders made of tubulin, a GTPase responsible for essential functions during cell growth and division, and thus, key target for anti-tumor drugs. In MTs, GTP hydrolysis triggers structural changes in the lattice, which are responsible for interaction with regulatory factors. The stabilizing GTP-cap is a hallmark of MTs and the mechanism of the chemical-structural link between the GTP hydrolysis site and the MT lattice is a matter of debate. We have analyzed the structure of tubulin and MTs assembled in the presence of fluoride salts that mimic the GTP-bound and GDP•Pi transition states. Our results challenge current models because tubulin does not change axial length upon GTP hydrolysis. Moreover, analysis of the structure of MTs assembled in the presence of several nucleotide analogues and of taxol allows us to propose that previously described lattice expansion could be a post-hydrolysis stage involved in Pi release.