Molecular investigations into the unfoldase action of severing enzymes on microtubules

Rohith A. Varikoti, Amanda C. Macke, Virginia Speck, Jennifer L. Ross, Ruxandra I. Dima

Research output: Contribution to journalArticle

Abstract

Microtubule (MT)-associated proteins regulate the dynamic behavior of MTs during cellular processes. MT severing enzymes are the associated proteins which destabilize MTs by removing subunits from the lattice. One model for how severing enzymes remove tubulin dimers from the MT lattice is by unfolding its subunits through pulling on the carboxy-terminal tails of tubulin dimers. This model stems from the fact that severing enzymes are AAA+ unfoldases. To test this mechanism, we apply pulling forces on the carboxy-terminal regions of MT subunits using coarse grained molecular simulations. In our simulations, we used different MT lattices and concentrations of severing enzymes. We compare our simulation results with data from in vitro severing assays and find that the experimental data is best fit by a model of cooperative removal of protofilament fragments by severing enzymes, which depends on the severing enzyme concentration and placement on the MT lattice.

Original languageEnglish (US)
Pages (from-to)214-228
Number of pages15
JournalCytoskeleton
Volume77
Issue number5-6
DOIs
StatePublished - May 1 2020

Keywords

  • carboxy terminal tail(s)
  • coarse-grained simulations
  • microtubule severing enzymes
  • microtubules
  • protofilaments

ASJC Scopus subject areas

  • Structural Biology
  • Cell Biology

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