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

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

Research output: Contribution to journalArticlepeer-review

50 Scopus citations

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.

Original languageAmerican English
Pages (from-to)195-203
Number of pages9
JournalNature Materials
Volume13
Issue number2
DOIs
StatePublished - Feb 2014

Bibliographical note

Funding Information:
C.R.S., Y.L. and P.A.K. were supported by DOE-BES DE-FG02-06ER46314 (dynamic evolution of assemblies) and NSF DMR-1101900 (protein phase behaviour). L.W. and H.P.M. were supported by NIH R01-NS13560. D.J.N. and U.R. were supported by the US–Israel Binational Foundation (Grant 2009271), and U.R. acknowledges support from the Israel Science Foundation (Grant 1372/13). M.A.O-L. was supported by Mexico-based science foundations CONACyT, PIFI, PROMEP and UCMEXUS. C.S. was supported by National Research Foundation of Korea Grant NRF 2011-355-C00037. M.C.C. was supported by National Research Foundation of Korea Grants NRF 2011-0031931, 2011-0030923, 2012R1A1A1011023 and KAIST HRHRP N10110077. C.R.S. acknowledges discussions with KAIST faculty as part of his WCU (World Class University) Visiting Professor of Physics appointment supported by the National Research Foundation of Korea funded by the Ministry of Education, Science and Technology No. R33-2008-000-10163-0. We acknowledge use of UC-Santa Barbara’s TEM bioimaging and NSF-DMR-MRSEC facilities (NSF-DMR-1121053, a member of the NSF-funded Materials Research Facilities Network www.mrfn.org), and the Stanford Synchrotron Radiation Laboratory (SSRL), a DOE National Laboratory (where the SAXS work was performed).

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