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Issue 47, 2010
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Vinblastine perturbation of tubulin protofilament structure: a computational insight

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Abstract

Tubulin is a heterodimeric protein whose self assembly leads to the formation of protofilaments and of more complex structures called microtubules, key components of the cytoskeleton which have a fundamental role in the cell division process. Due to its biological function, tubulin is the target of many antitumoral molecules that exert their action on proliferating tumoral cells. Among these drugs, vinblastine has been widely used in therapy for a long time, albeit its mechanism of interaction with tubulin has remained elusive until recently. Vinblastine acts as a microtubule destabilizing agent and induces the formation of curved or ring-shaped tubulin polymers instead of linear protofilaments in vitro. In this paper we compare, using molecular dynamics simulations and free energy calculations, the network of interactions that allow the assembly of model linear protofilaments with those present in curved tubulin polymers complexed with vinblastine. It is shown that vinblastine, wedging between tubulin heterodimers, actually mediates part of the interactions between them and acts by crosslinking the two proteins, leading to the observed curved polymers rather than to their disassembly.

Graphical abstract: Vinblastine perturbation of tubulin protofilament structure: a computational insight

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Publication details

The article was received on 17 May 2010, accepted on 03 Sep 2010 and first published on 26 Oct 2010


Article type: Paper
DOI: 10.1039/C0CP00594K
Phys. Chem. Chem. Phys., 2010,12, 15530-15536

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    Vinblastine perturbation of tubulin protofilament structure: a computational insight

    S. Rendine, S. Pieraccini and M. Sironi, Phys. Chem. Chem. Phys., 2010, 12, 15530
    DOI: 10.1039/C0CP00594K

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