Skip to Main content Skip to Navigation
New interface
Journal articles

The state of the guanosine nucleotide allosterically affects the interfaces of tubulin in protofilament

Abstract : The dynamics of microtubules is essential for many microtubule-dependent cellular functions such as the mitosis. It has been recognized for a long time that GTP hydrolysis in αβ-tubulin polymers plays a critical role in this dynamics. However, the effects of the changes in the nature of the guanosine nucleotide at the E-site in β-tubulin on microtubule structure and stability are still not well understood. In the present work, we performed all-atom molecular dynamics simulations of a αβα-tubulin heterotrimer harboring a guanosine nucleotide in three different states at the E-site: GTP, GDP-Pi and GDP. We found that changes in the nucleotide state is associated with significant conformational variations at the α-tubulin N- and β-tubulin M-loops which impact the interactions between tubulin protofilaments. The results also show that GTP hydrolysis reduces αβ-tubulin interdimer contacts in favor of intradimer interface. From an atomistic point view, we propose a role for α-tubulin glutamate residue 254 in catalytic magnesium coordination and identified a water molecule in the nucleotide binding pocket which is most probably required for nucleotide hydrolysis. Finally, the results are discussed with reference to the role of taxol in microtubule stability and the recent tubulin-sT2R crystal structures.
Document type :
Journal articles
Complete list of metadata
Contributor : Olek Maciejak Connect in order to contact the contributor
Submitted on : Thursday, September 19, 2019 - 3:13:00 PM
Last modification on : Saturday, June 25, 2022 - 9:02:38 PM

Links full text



Joseph André, Marie-Jeanne Clément, Elisabeth Adjadj, Flavio Toma, Patrick Curmi, et al.. The state of the guanosine nucleotide allosterically affects the interfaces of tubulin in protofilament. Journal of Computer-Aided Molecular Design, 2012, 26 (4), pp.397-407. ⟨10.1007/s10822-012-9566-x⟩. ⟨hal-02292225⟩



Record views