Catastrophic depolymerization of microtubules driven by subunit shape change

Bollinger, Jonathan A.; Stevens, Mark J.

doi:10.1039/C7SM02033C

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:

^[1]; Stevens, Mark J. ^[1]

Sandia National Lab. (SNL-NM), Albuquerque, NM (United States). Center for Integrated Nanotechnologies

Publication Date:: Wed Jan 17 00:00:00 EST 2018

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:: 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.

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                    Bollinger, Jonathan A., & Stevens, Mark J. Catastrophic depolymerization of microtubules driven by subunit shape change.  United States.  https://doi.org/10.1039/C7SM02033C

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                    Bollinger, Jonathan A., and Stevens, Mark J. Wed .  
"Catastrophic depolymerization of microtubules driven by subunit shape change".  United States.  https://doi.org/10.1039/C7SM02033C.  https://www.osti.gov/servlets/purl/1441468.

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@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}

}

Copy to clipboard

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https://doi.org/10.1039/C7SM02033C

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Cited by: 9 works

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Fig. 1: (a) Illustration of the cyclical dynamic instability of microtubules (MTs), which is controlled by GTP-GDP switching on the β-subunit of αβ-tubulin. We focus on the portion of the cycle where it is hypothesized that dephosphorylation drives depolymerization by inducing lattice dimers to change shape. (b-c) Illustrations of themore »

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Works referenced in this record:

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Similar Records

Title: Catastrophic depolymerization of microtubules driven by subunit shape change

Abstract

Citation Formats

Figures / Tables:

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

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