Atomistic Basis of Microtubule Dynamic Instability Assessed Via Multiscale Modeling.

ABSTRACT: Microtubule "dynamic instability," the abrupt switching from assembly to disassembly caused by the hydrolysis of GTP to GDP within the β subunit of the αβ-tubulin heterodimer, is necessary for vital cellular processes such as mitosis and migration. Despite existing high-resolution structural data, the key mechanochemical differences between the GTP and GDP states that mediate dynamic instability behavior remain unclear. Starting with a published atomic-level structure as an input, we used multiscale modeling to find that GTP hydrolysis results in both longitudinal bond weakening (~ 4 k_BT) and an outward bending preference (~ 1.5 k_BT) to both drive dynamic instability and give rise to the microtubule tip structures previously observed by light and electron microscopy.

SUBMITTER: Hemmat M 

PROVIDER: S-EPMC8302526 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature