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Biophysical Journal
Article
License: Elsevier Non-Commercial
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Biophysical Journal
Article . 2020 . Peer-reviewed
License: Elsevier Non-Commercial
Data sources: Crossref
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Microtubule Simulations Provide Insight into the Molecular Mechanism Underlying Dynamic Instability

Authors: Dudu, Tong; Gregory A, Voth;

Microtubule Simulations Provide Insight into the Molecular Mechanism Underlying Dynamic Instability

Abstract

The dynamic instability of microtubules (MTs), which refers to their ability to switch between polymerization and depolymerization states, is crucial for their function. It has been proposed that the growing MT ends are protected by a "GTP cap" that consists of GTP-bound tubulin dimers. When the speed of GTP hydrolysis is faster than dimer recruitment, the loss of this GTP cap will lead the MT to undergo rapid disassembly. However, the underlying atomistic mechanistic details of the dynamic instability remains unclear. In this study, we have performed long-time atomistic molecular dynamics simulations (1 μs for each system) for MT patches as well as a short segment of a closed MT in both GTP- and GDP-bound states. Our results confirmed that MTs in the GDP state generally have weaker lateral interactions between neighboring protofilaments (PFs) and less cooperative outward bending conformational change, where the difference between bending angles of neighboring PFs tends to be larger compared with GTP ones. As a result, when the GDP state tubulin dimer is exposed at the growing MT end, these factors will be more likely to cause the MT to undergo rapid disassembly. We also compared simulation results between the special MT seam region and the remaining material and found that the lateral interactions between MT PFs at the seam region were comparatively much weaker. This finding is consistent with the experimental suggestion that the seam region tends to separate during the disassembly process of an MT.

Keywords

Tubulin, Guanosine Triphosphate, Molecular Dynamics Simulation, Guanosine Diphosphate, Microtubules

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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
33
Top 10%
Average
Top 10%
hybrid