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Catastrophic depolymerization of microtubules driven by subunit shape change

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Abstract

Microtubules exhibit a dynamic instability between growth and catastrophic depolymerization. GTP-tubulin (αβ-dimer bound to GTP) self-assembles, but dephosphorylation of GTP- to GDP-tubulin within the tubule results in destabilization. While the mechanical basis for destabilization is not fully understood, one hypothesis is that dephosphorylation causes tubulin to change shape, frustrating bonds and generating stress. To test this idea, we perform molecular dynamics simulations of microtubules built from coarse-grained models of tubulin, incorporating a small compression of α-subunits associated with dephosphorylation in experiments. We find that this shape change induces depolymerization of otherwise stable systems via unpeeling “ram's horns” characteristic of microtubules. Depolymerization can be averted by caps with uncompressed α-subunits, i.e., GTP-rich end regions. Thus, the shape change is sufficient to yield microtubule behavior.

Graphical abstract: Catastrophic depolymerization of microtubules driven by subunit shape change

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Publication details

The article was received on 13 Oct 2017, accepted on 16 Jan 2018 and first published on 17 Jan 2018


Article type: Communication
DOI: 10.1039/C7SM02033C
Citation: Soft Matter, 2018, Advance Article
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    Catastrophic depolymerization of microtubules driven by subunit shape change

    J. A. Bollinger and M. J. Stevens, Soft Matter, 2018, Advance Article , DOI: 10.1039/C7SM02033C

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