Catastrophic depolymerization of microtubules driven by subunit shape change
- Sandia National Lab. (SNL-NM), Albuquerque, NM (United States). Center for Integrated Nanotechnologies
We report that 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.
- Research Organization:
- Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)
- Sponsoring Organization:
- USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22). Materials Sciences & Engineering Division; USDOE National Nuclear Security Administration (NNSA)
- Grant/Contract Number:
- AC04-94AL85000; NA0003525
- OSTI ID:
- 1441468
- Report Number(s):
- SAND-2018-4152J; SMOABF; 662771
- Journal Information:
- Soft Matter, Vol. 14, Issue 10; ISSN 1744-683X
- Publisher:
- Royal Society of ChemistryCopyright Statement
- Country of Publication:
- United States
- Language:
- English
Web of Science
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