Cell Systems
Volume 11, Issue 6, 16 December 2020, Pages 608-624.e9
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Article
Dynamic Instability from Non-equilibrium Structural Transitions on the Energy Landscape of Microtubule

https://doi.org/10.1016/j.cels.2020.09.008Get rights and content
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Highlights

  • Dynamic instability is fully explained by kinetics of tubulin conformational changes

  • Catastrophe and shortening are controlled by straight-to-curved transition of tubulins

  • Rescue is the reverse of catastrophe

  • Minus end follows different kinetic pathways for tubulin conformational changes

Summary

Microtubules are the backbone of the cytoskeleton and vital to numerous cellular processes. The central dogma of microtubules is that all their functions are driven by dynamic instability, but its mechanism has remained unresolved for over 30 years because of conceptual difficulties inherent in the dominant GTP-cap framework. We present a physically rigorous structural mechanochemical model: dynamic instability is driven by non-equilibrium transitions between the bent (B), straight (S), and curved (C) forms of tubulin monomers and longitudinal interfaces in the two-dimensional lattice of microtubule. All the different phenomena (growth, shortening, catastrophe, rescue, and pausing) are controlled by the kinetic pathways for BSC transitions and corresponding energy landscapes. Different kinetics at minus end are due to different BSC pathways imposed by the polarity of microtubule lattice. This model enables us to reproduce all the observed phenomena of dynamic instability of purified tubulins in kinetic simulations.

Keywords

microtubule
dynamic instability
protein dynamics
conformational dynamics
energy landscape
mechanochemical model
non-equilibrium
emergent phenomena
structural model
tubulin

Cited by (0)

2

Present address: Quantum-Si Incorporated, 530 Old Whitfield St., Guilford, CT 06437, USA

3

Lead Contact