Diverse balances of tubulin interactions and shape change drive and interrupt microtubule depolymerization
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. Finally, the results demonstrate a mechanism by which microtubule rescue can occur.
- Publication Date:
- Research Org.:
- Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)
- Sponsoring Org.:
- USDOE Office of Science (SC), Basic Energy Sciences (BES)
- OSTI Identifier:
- 1595025
- Alternate Identifier(s):
- OSTI ID: 1569780
- Report Number(s):
- SAND-2019-15010J
Journal ID: ISSN 1744-683X; SMOABF; 682259
- Grant/Contract Number:
- AC04-94AL85000; NA0003525; KC0203010
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Soft Matter
- Additional Journal Information:
- Journal Volume: 15; Journal Issue: 40; Journal ID: ISSN 1744-683X
- Publisher:
- Royal Society of Chemistry
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 77 NANOSCIENCE AND NANOTECHNOLOGY
Citation Formats
Bollinger, Jonathan A., and Stevens, Mark J. Diverse balances of tubulin interactions and shape change drive and interrupt microtubule depolymerization. United States: N. p., 2019.
Web. doi:10.1039/C9SM01323G.
Bollinger, Jonathan A., & Stevens, Mark J. Diverse balances of tubulin interactions and shape change drive and interrupt microtubule depolymerization. United States. https://doi.org/10.1039/C9SM01323G
Bollinger, Jonathan A., and Stevens, Mark J. Tue .
"Diverse balances of tubulin interactions and shape change drive and interrupt microtubule depolymerization". United States. https://doi.org/10.1039/C9SM01323G. https://www.osti.gov/servlets/purl/1595025.
@article{osti_1595025,
title = {Diverse balances of tubulin interactions and shape change drive and interrupt microtubule depolymerization},
author = {Bollinger, Jonathan A. and Stevens, Mark J.},
abstractNote = {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. Finally, the results demonstrate a mechanism by which microtubule rescue can occur.},
doi = {10.1039/C9SM01323G},
journal = {Soft Matter},
number = 40,
volume = 15,
place = {United States},
year = {Tue Oct 08 00:00:00 EDT 2019},
month = {Tue Oct 08 00:00:00 EDT 2019}
}
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