Microtubule instability driven by longitudinal and lateral strain propagation

PLoS Comput Biol. 2020 Sep 2;16(9):e1008132. doi: 10.1371/journal.pcbi.1008132. eCollection 2020 Sep.

Abstract

Tubulin dimers associate longitudinally and laterally to form metastable microtubules (MTs). MT disassembly is preceded by subtle structural changes in tubulin fueled by GTP hydrolysis. These changes render the MT lattice unstable, but it is unclear exactly how they affect lattice energetics and strain. We performed long-time atomistic simulations to interrogate the impacts of GTP hydrolysis on tubulin lattice conformation, lateral inter-dimer interactions, and (non-)local lateral coordination of dimer motions. The simulations suggest that most of the hydrolysis energy is stored in the lattice in the form of longitudinal strain. While not significantly affecting lateral bond stability, the stored elastic energy results in more strongly confined and correlated dynamics of GDP-tubulins, thereby entropically destabilizing the MT lattice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Guanosine Triphosphate / chemistry
  • Guanosine Triphosphate / metabolism
  • Hydrolysis
  • Microtubules* / chemistry
  • Microtubules* / metabolism
  • Microtubules* / physiology
  • Molecular Dynamics Simulation
  • Protein Conformation
  • Thermodynamics
  • Tubulin* / chemistry
  • Tubulin* / metabolism
  • Tubulin* / physiology

Substances

  • Tubulin
  • Guanosine Triphosphate

Grants and funding

The work was supported by the Max Planck Society (MI and HG) and the German Research Foundation via the grant IG 109/1-1 (awarded to MI). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.