1. Structural Biology and Molecular Biophysics
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Microtubule assembly governed by tubulin allosteric gain in flexibility and lattice induced fit

  1. Maxim Igaev  Is a corresponding author
  2. Helmut Grubmüller  Is a corresponding author
  1. Max Planck Institute for Biophysical Chemistry, Germany
Research Article
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Cite as: eLife 2018;7:e34353 doi: 10.7554/eLife.34353

Abstract

Microtubules (MTs) are key components of the cytoskeleton and play a central role in cell division and development. MT assembly is known to be associated with a structural change in αβ-tubulin dimers from kinked to straight conformations. How GTP binding renders individual dimers polymerization-competent, however, is still unclear. Here, we have characterized the conformational dynamics and energetics of unassembled tubulin using atomistic molecular dynamics and free energy calculations. Contradictory to existing allosteric and lattice models, we find that GTP-tubulin favors a broad range of almost isoenergetic curvatures, whereas GDP-tubulin has a much lower bending flexibility. Moreover, irrespective of the bound nucleotide and curvature, two conformational states exist differing in location of the anchor point connecting the monomers that affects tubulin bending, with one state being strongly favored in solution. Our findings suggest a new combined model in which MTs incorporate and stabilize flexible GTP-dimers with a specific anchor point state.

Article and author information

Author details

  1. Maxim Igaev

    Department of Theoretical and Computational Biophysics, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany
    For correspondence
    migaev@mpibpc.mpg.de
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon 0000-0001-8781-1604
  2. Helmut Grubmüller

    Department of Theoretical and Computational Biophysics, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany
    For correspondence
    hgrubmu@gwdg.de
    Competing interests
    The authors declare that no competing interests exist.

Funding

Max Planck Society (Open-access funding)

  • Maxim Igaev
  • Helmut Grubmüller

Deutsche Forschungsgemeinschaft (IG 109/1-1)

  • Maxim Igaev

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Luke M Rice, Reviewing Editor, UT Southwestern Medical Cetner, United States

Publication history

  1. Received: December 14, 2017
  2. Accepted: April 12, 2018
  3. Accepted Manuscript published: April 13, 2018 (version 1)

Copyright

© 2018, Igaev & Grubmüller

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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