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

Journal Article · · Soft Matter
DOI:https://doi.org/10.1039/C9SM01323G· OSTI ID:1595025
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.
Research Organization:
Sandia National Laboratories (SNL-NM), Albuquerque, NM (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22)
Grant/Contract Number:
AC04-94AL85000; NA0003525
OSTI ID:
1595025
Alternate ID(s):
OSTI ID: 1569780
Report Number(s):
SAND--2019-15010J; 682259
Journal Information:
Soft Matter, Journal Name: Soft Matter Journal Issue: 40 Vol. 15; ISSN SMOABF; ISSN 1744-683X
Publisher:
Royal Society of ChemistryCopyright Statement
Country of Publication:
United States
Language:
English

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