skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Catastrophic depolymerization of microtubules driven by subunit shape change

Journal Article · · Soft Matter
DOI:https://doi.org/10.1039/C7SM02033C· OSTI ID:1441468

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
Citation Metrics:
Cited by: 9 works
Citation information provided by
Web of Science

References (32)

EBs Recognize a Nucleotide-Dependent Structural Cap at Growing Microtubule Ends journal April 2012
Microtubule Elasticity: Connecting All-Atom Simulations with Continuum Mechanics journal January 2010
Nucleotide-dependent bending flexibility of tubulin regulates microtubule assembly journal June 2005
Nanomechanics of Microtubules journal November 2002
Deformation and Collapse of Microtubules on the Nanometer Scale journal August 2003
Structural Plasticity in Actin and Tubulin Polymer Dynamics journal August 2009
Self-assembly of artificial microtubules journal January 2012
Dynamic instability of microtubule growth journal November 1984
DNA sequence–directed shape change of photopatterned hydrogels via high-degree swelling journal September 2017
Estimates of lateral and longitudinal bond energies within the microtubule lattice journal April 2002
Tubulin Bond Energies and Microtubule Biomechanics Determined from Nanoindentation in Silico journal November 2014
High-Resolution Microtubule Structures Reveal the Structural Transitions in αβ-Tubulin upon GTP Hydrolysis journal May 2014
Fast Parallel Algorithms for Short-Range Molecular Dynamics journal March 1995
Microtubule Dynamics Depart from the Wormlike Chain Model journal January 2008
Mechanistic Origin of Microtubule Dynamic Instability and Its Modulation by EB Proteins journal August 2015
Theoretical Analysis of Microtubule Dynamics at All Times journal November 2014
Structural Microtubule Cap: Stability, Catastrophe, Rescue, andThird State journal September 2002
Structure of growing microtubule ends: two-dimensional sheets close into tubes at variable rates journal June 1995
The Dam1 kinetochore ring complex moves processively on depolymerizing microtubule ends journal January 2006
Thermal fluctuations of grafted microtubules provide evidence of a length-dependent persistence length journal June 2006
Rapid Microtubule Self-Assembly Kinetics journal August 2011
Structural changes at microtubule ends accompanying GTP hydrolysis: Information from a slowly hydrolyzable analogue of GTP, guanylyl ( , )methylenediphosphonate journal March 1998
Microtubule dynamics and microtubule caps: a time-resolved cryo- electron microscopy study journal September 1991
Molecular and Mechanical Causes of Microtubule Catastrophe and Aging journal December 2015
Structure of the αβ tubulin dimer by electron crystallography journal January 1998
Insight into tubulin regulation from a complex with colchicine and a stathmin-like domain journal March 2004
Microtubule dynamics and microtubule caps: a time-resolved cryo-electron microscopy study journal December 1991
Rapid Microtubule Self-Assembly Kinetics journal September 2014
Microtubule elasticity: Connecting all-atom simulations with continuum mechanics journal February 2009
Self-assembly of artificial microtubules text January 2012
Self-assembly of Chiral Tubules text January 2013
Tubulin bond energies and microtubule biomechanics determined from nanoindentation in silico text January 2015

Figures / Tables (11)