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Title: Catastrophic depolymerization of microtubules driven by subunit shape change

Abstract

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.

Authors:
ORCiD logo [1];  [1]
  1. Sandia National Lab. (SNL-NM), Albuquerque, NM (United States). Center for Integrated Nanotechnologies
Publication Date:
Research Org.:
Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22). Materials Sciences & Engineering Division; USDOE National Nuclear Security Administration (NNSA)
OSTI Identifier:
1441468
Report Number(s):
SAND-2018-4152J
Journal ID: ISSN 1744-683X; SMOABF; 662771
Grant/Contract Number:  
AC04-94AL85000; NA0003525
Resource Type:
Journal Article: Accepted Manuscript
Journal Name:
Soft Matter
Additional Journal Information:
Journal Volume: 14; Journal Issue: 10; Journal ID: ISSN 1744-683X
Publisher:
Royal Society of Chemistry
Country of Publication:
United States
Language:
English
Subject:
77 NANOSCIENCE AND NANOTECHNOLOGY; 37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY

Citation Formats

Bollinger, Jonathan A., and Stevens, Mark J. Catastrophic depolymerization of microtubules driven by subunit shape change. United States: N. p., 2018. Web. doi:10.1039/C7SM02033C.
Bollinger, Jonathan A., & Stevens, Mark J. Catastrophic depolymerization of microtubules driven by subunit shape change. United States. doi:10.1039/C7SM02033C.
Bollinger, Jonathan A., and Stevens, Mark J. Wed . "Catastrophic depolymerization of microtubules driven by subunit shape change". United States. doi:10.1039/C7SM02033C.
@article{osti_1441468,
title = {Catastrophic depolymerization of microtubules driven by subunit shape change},
author = {Bollinger, Jonathan A. and Stevens, Mark J.},
abstractNote = {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.},
doi = {10.1039/C7SM02033C},
journal = {Soft Matter},
number = 10,
volume = 14,
place = {United States},
year = {Wed Jan 17 00:00:00 EST 2018},
month = {Wed Jan 17 00:00:00 EST 2018}
}

Journal Article:
Free Publicly Available Full Text
This content will become publicly available on January 17, 2019
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Cited by: 1 work
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