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

Elisabeth A. Geyer, Alexander Burns, Beth A. Lalonde, Xuecheng Ye, Felipe Andres Piedra, Tim C. Huffaker, Luke M. Rice

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Microtubule dynamic instability depends on the GTPase activity of the polymerizing ab-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.

Original languageEnglish (US)
Article numbere10113
JournaleLife
Volume4
Issue numberOCTOBER2015
DOIs
StatePublished - Oct 6 2015

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GTP Phosphohydrolases
Tubulin
Microtubules
Mutation
Conformations
Guanosine Triphosphate
Hydrolysis

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Medicine(all)
  • Neuroscience(all)

Cite this

Geyer, E. A., Burns, A., Lalonde, B. A., Ye, X., Piedra, F. A., Huffaker, T. C., & Rice, L. M. (2015). A mutation uncouples the tubulin conformational and GTPase cycles, revealing allosteric control of microtubule dynamics. eLife, 4(OCTOBER2015), [e10113]. https://doi.org/10.7554/eLife.10113

A mutation uncouples the tubulin conformational and GTPase cycles, revealing allosteric control of microtubule dynamics. / Geyer, Elisabeth A.; Burns, Alexander; Lalonde, Beth A.; Ye, Xuecheng; Piedra, Felipe Andres; Huffaker, Tim C.; Rice, Luke M.

In: eLife, Vol. 4, No. OCTOBER2015, e10113, 06.10.2015.

Research output: Contribution to journalArticle

Geyer EA, Burns A, Lalonde BA, Ye X, Piedra FA, Huffaker TC et al. A mutation uncouples the tubulin conformational and GTPase cycles, revealing allosteric control of microtubule dynamics. eLife. 2015 Oct 6;4(OCTOBER2015). e10113. https://doi.org/10.7554/eLife.10113
Geyer, Elisabeth A. ; Burns, Alexander ; Lalonde, Beth A. ; Ye, Xuecheng ; Piedra, Felipe Andres ; Huffaker, Tim C. ; Rice, Luke M. / A mutation uncouples the tubulin conformational and GTPase cycles, revealing allosteric control of microtubule dynamics. In: eLife. 2015 ; Vol. 4, No. OCTOBER2015.
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