Catastrophic depolymerization of microtubules driven by subunit shape change

JA Bollinger and MJ Stevens, SOFT MATTER, 14, 1748-1752 (2018).

DOI: 10.1039/c7sm02033c

Microtubules exhibit a dynamic instability between growth and catastrophic depolymerization. GTP-tubulin (alpha beta-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 alpha-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 alpha-subunits, i.e., GTP-rich end regions. Thus, the shape change is sufficient to yield microtubule behavior.

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