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Diverse balances of tubulin interactions and shape change drive and interrupt microtubule depolymerization

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Abstract

Microtubules are stiff biopolymers that self-assemble via the addition of GTP-tubulin (αβ-dimer bound to GTP), but hydrolysis of GTP- to GDP-tubulin within the tubules destabilizes them toward catastrophically-fast depolymerization. The molecular mechanisms and features of the individual tubulin proteins that drive such behavior are still not well-understood. Using molecular dynamics simulations of whole microtubules built from a coarse-grained model of tubulin, we demonstrate how conformational shape changes (i.e., deformations) in subunits that frustrate tubulin–tubulin binding within microtubules drive depolymerization of stiff tubules via unpeeling “ram's horns” consistent with experiments. We calculate the sensitivity of these behaviors to the length scales and strengths of binding attractions and varying degrees of binding frustration driven by subunit shape change, and demonstrate that the dynamic instability and mechanical properties of microtubules can be produced based on either balanced or imbalanced strengths of lateral and vertical binding attractions. Finally, we show how catastrophic depolymerization can be interrupted by small regions of the microtubule containing undeformed dimers, corresponding to incomplete lattice hydrolysis. The results demonstrate a mechanism by which microtubule rescue can occur.

Graphical abstract: Diverse balances of tubulin interactions and shape change drive and interrupt microtubule depolymerization

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Publication details

The article was received on 02 Jul 2019, accepted on 20 Sep 2019 and first published on 08 Oct 2019


Article type: Paper
DOI: 10.1039/C9SM01323G
Soft Matter, 2019, Advance Article

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    Diverse balances of tubulin interactions and shape change drive and interrupt microtubule depolymerization

    J. A. Bollinger and M. J. Stevens, Soft Matter, 2019, Advance Article , DOI: 10.1039/C9SM01323G

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