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Elife. 2015 Oct 6;4:e10113. doi: 10.7554/eLife.10113.

A mutation uncouples the tubulin conformational and GTPase cycles, revealing allosteric control of microtubule dynamics.

Author information

1
Departments of Biophysics and Biochemistry, University of Texas Southwestern Medical Center, Dallas, United States.
2
Department of Molecular Biology and Genetics, Cornell University, Ithaca, United States.

Abstract

Microtubule dynamic instability depends on the GTPase activity of the polymerizing αβ-tubulin subunits, which cycle through at least three distinct conformations as they move into and out of microtubules. How this conformational cycle contributes to microtubule growing, shrinking, and switching remains unknown. Here, we report that a buried mutation in αβ-tubulin yields microtubules with dramatically reduced shrinking rate and catastrophe frequency. The mutation causes these effects by suppressing a conformational change that normally occurs in response to GTP hydrolysis in the lattice, without detectably changing the conformation of unpolymerized αβ-tubulin. Thus, the mutation weakens the coupling between the conformational and GTPase cycles of αβ-tubulin. By showing that the mutation predominantly affects post-GTPase conformational and dynamic properties of microtubules, our data reveal that the strength of the allosteric response to GDP in the lattice dictates the frequency of catastrophe and the severity of rapid shrinking.

KEYWORDS:

S. cerevisiae; allostery; biophysics; cell biology; conformation; dynamics; microtubule; structural biology; tubulin

PMID:
26439009
PMCID:
PMC4728127
DOI:
10.7554/eLife.10113
[Indexed for MEDLINE]
Free PMC Article

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