Insights into allosteric control of microtubule dynamics from a buried β-tubulin mutation that causes faster growth and slower shrinkage

Xuecheng Ye, Tae Kim, Elisabeth A. Geyer, Luke M. Rice

Research output: Contribution to journalArticle

Abstract

αβ-tubulin subunits cycle through a series of different conformations in the polymer lattice during microtubule growing and shrinking. How these allosteric responses to different tubulin:tubulin contacts contribute to microtubule dynamics, and whether the contributions are evolutionarily conserved, remains poorly understood. Here, we sought to determine whether the microtubule-stabilizing effects (slower shrinking) of the β:T238A mutation we previously observed using yeast αβ-tubulin would generalize to mammalian microtubules. Using recombinant human microtubules as a model, we found that the mutation caused slow microtubule shrinking, indicating that this effect of the mutation is indeed conserved. However, unlike in yeast, β:T238A human microtubules grew faster than wild-type and the mutation did not appear to attenuate the conformational change associated with guanosine 5′-triphosphate (GTP) hydrolysis in the lattice. We conclude that the assembly-dependent conformational change in αβ-tubulin can contribute to determine the rates of microtubule growing as well as shrinking. Our results also suggest that an allosteric perturbation like the β:T238A mutation can alter the behavior of terminal subunits without accompanying changes in the conformation of fully surrounded subunits in the body of the microtubule.

Original languageEnglish (US)
Pages (from-to)1429-1439
Number of pages11
JournalProtein Science
Volume29
Issue number6
DOIs
StatePublished - Jun 1 2020

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

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