MilliporeSigma
  • Transformation of taxol-stabilized microtubules into inverted tubulin tubules triggered by a tubulin conformation switch.

Transformation of taxol-stabilized microtubules into inverted tubulin tubules triggered by a tubulin conformation switch.

Nature materials (2014-01-21)
Miguel A Ojeda-Lopez, Daniel J Needleman, Chaeyeon Song, Avi Ginsburg, Phillip A Kohl, Youli Li, Herbert P Miller, Leslie Wilson, Uri Raviv, Myung Chul Choi, Cyrus R Safinya
ABSTRACT

Bundles of taxol-stabilized microtubules (MTs)--hollow tubules comprised of assembled αβ-tubulin heterodimers--spontaneously assemble above a critical concentration of tetravalent spermine and are stable over long times at room temperature. Here we report that at concentrations of spermine several-fold higher the MT bundles (B(MT)) quickly become unstable and undergo a shape transformation to bundles of inverted tubulin tubules (B(ITT)), the outside surface of which corresponds to the inner surface of the B(MT) tubules. Using transmission electron microscopy and synchrotron small-angle X-ray scattering, we quantitatively determined both the nature of the B(MT)-to-B(ITT) transformation pathway, which results from a spermine-triggered conformation switch from straight to curved in the constituent taxol-stabilized tubulin oligomers, and the structure of the B(ITT) phase, which is formed of tubules of helical tubulin oligomers. Inverted tubulin tubules provide a platform for studies requiring exposure and availability of the inside, luminal surface of MTs to MT-targeted drugs and MT-associated proteins.

MATERIALS
Product Number
Brand
Product Description

Paclitaxel semi-synthetic for peak identification, European Pharmacopoeia (EP) Reference Standard
Paclitaxel, European Pharmacopoeia (EP) Reference Standard
Paclitaxel semi-synthetic for system suitability, European Pharmacopoeia (EP) Reference Standard
Sigma-Aldrich
Paclitaxel, from Taxus brevifolia, ≥95% (HPLC), powder
Sigma-Aldrich
Paclitaxel, from semisynthetic, ≥98%
Sigma-Aldrich
Paclitaxel, from Taxus yannanensis, powder