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• W2897880573 abstract "Abstract Microtubules are cylindrical polymers of αβ-tubulin that play critical roles in fundamental processes like chromosome segregation and vesicular transport. Microtubules display dynamic instability, switching stochastically between growing and rapid shrinking as a consequence of GTPase activity in the lattice. The molecular mechanisms behind microtubule catastrophe, the switch from growing 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 αβ-tubulin incorrectly predict the concentration-dependence of microtubule catastrophe. Recent studies provided evidence for three distinct conformations of αβ-tubulin in the lattice that likely correspond to GTP, GDP.P i , and GDP. The incommensurate lattices observed for these different conformations raises the possibility that in a mixed nucleotide state lattice, neighboring tubulin dimers might modulate each other’s conformations and hence their biochemistry. We explored whether incorporating a GDP.P i state or the likely effects of conformational accommodation can improve predictions of catastrophe. Adding a GDP.P i intermediate did not improve the model. In contrast, adding neighbor-dependent modulation of tubulin biochemistry improved predictions of catastrophe. Conformational accommodation should propagate beyond nearest-neighbor contacts, and consequently our modeling demonstrates that long-range, through-lattice effects are important determinants of microtubule catastrophe." @default.
• W2897880573 created "2018-10-26" @default.
• W2897880573 creator A5004300224 @default.
• W2897880573 creator A5056334757 @default.
• W2897880573 date "2018-10-14" @default.
• W2897880573 modified "2023-09-25" @default.
• W2897880573 title "A role for long-range, through-lattice coupling in microtubule catastrophe" @default.
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• W2897880573 doi "https://doi.org/10.1101/443283" @default.
• W2897880573 hasPublicationYear "2018" @default.
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