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

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Bundles of taxol-stabilized microtubules (MTs)-hollow tubules comprised of assembled alpha beta-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.
Publisher
NATURE PUBLISHING GROUP
Issue Date
2014-02
Language
English
Article Type
Article
Keywords

SYNCHROTRON X-RAY; CRYOELECTRON MICROSCOPY; ALZHEIMERS-DISEASE; PURIFIED TUBULIN; TAU; DYNAMICS; RINGS; FORM; DNA; PROTOFILAMENTS

Citation

NATURE MATERIALS, v.13, no.2, pp.195 - 203

ISSN
1476-1122
DOI
10.1038/nmat3858
URI
http://hdl.handle.net/10203/187421
Appears in Collection
BiS-Journal Papers(저널논문)
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