Unknown

Dataset Information

0

Long-range, through-lattice coupling improves predictions of microtubule catastrophe.


ABSTRACT: Microtubules are cylindrical polymers of ??-tubulin that play critical roles in fundamental processes such as chromosome segregation and vesicular transport. Microtubules display dynamic instability, switching stochastically between growth and rapid shrinking as a consequence of GTPase activity in the lattice. The molecular mechanisms behind microtubule catastrophe, the switch from growth to rapid shrinking, remain poorly defined. Indeed, two-state stochastic models that seek to describe microtubule dynamics purely in terms of the biochemical properties of GTP- and GDP-bound ??-tubulin predict the concentration dependence of microtubule catastrophe incorrectly. Recent studies provide evidence for three distinct conformations of ??-tubulin in the lattice that likely correspond to GTP, GDP.Pi, and GDP. The incommensurate lattices observed for these different conformations raise the possibility that in a mixed nucleotide state lattice, neighboring tubulin dimers might modulate each other's conformations and hence each other's biochemistry. We explored whether incorporating a GDP.Pi state or the likely effects of conformational accommodation can improve predictions of catastrophe. Adding a GDP.Pi intermediate did not improve the model. In contrast, adding neighbor-dependent modulation of tubulin biochemistry improved predictions of catastrophe. Because this conformational accommodation should propagate beyond nearest-neighbor contacts, our modeling suggests that long-range, through-lattice effects are important determinants of microtubule catastrophe.

SUBMITTER: Kim T 

PROVIDER: S-EPMC6724698 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

altmetric image

Publications

Long-range, through-lattice coupling improves predictions of microtubule catastrophe.

Kim Tae T   Rice Luke M LM  

Molecular biology of the cell 20190403 12


Microtubules are cylindrical polymers of αβ-tubulin that play critical roles in fundamental processes such as chromosome segregation and vesicular transport. Microtubules display dynamic instability, switching stochastically between growth and rapid shrinking as a consequence of GTPase activity in the lattice. The molecular mechanisms behind microtubule catastrophe, the switch from growth to rapid shrinking, remain poorly defined. Indeed, two-state stochastic models that seek to describe microtu  ...[more]

Similar Datasets

| S-EPMC8713758 | biostudies-literature
| S-EPMC6510489 | biostudies-literature
| S-EPMC8327381 | biostudies-literature
| S-EPMC5458152 | biostudies-literature
| S-EPMC4687879 | biostudies-literature
| S-EPMC5935067 | biostudies-literature
| S-EPMC5472782 | biostudies-literature
| S-EPMC4799368 | biostudies-literature
| S-EPMC3922448 | biostudies-literature
| S-EPMC6924994 | biostudies-literature