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.
Highlights
IntroductionThe funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
The dynamic nature of microtubules, long and hollow tubes formed by αβ-tubulin proteins, is crucial for their function is cells, and its precise characterization has been a longstanding problem for cell scientists
We investigate the behavior of tubulin dimers in a microtubule-like environment using extensive atomistic simulations and show that tubulins locked in the microtubule operate as both ‘loadable springs’ and ‘conformational switches’, tightly controlled by their surrounding neighbours
Summary
The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
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