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Taxol acts differently on different tubulin isotypes
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Chew, Yean Ming and Cross, Robert A. (2023) Taxol acts differently on different tubulin isotypes. Communications Biology, 6 . 946. doi:10.1038/s42003-023-05306-y |
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WRAP-taxol-acts-differently-different-tubulin-isotypes-Cross-2023.pdf - Published Version - Requires a PDF viewer. Available under License Creative Commons Attribution 4.0. Download (7Mb) | Preview |
Official URL: https://www.nature.com/articles/s42003-023-05306-y
Abstract
Taxol is a small molecule effector that allosterically locks tubulin into the microtubule lattice. We show here that taxol has different effects on different single-isotype microtubule lattices. Using in vitro reconstitution, we demonstrate that single-isotype α1β4 GDP-tubulin lattices are stabilised and expanded by 10 μM taxol, as reported by accelerated microtubule gliding in kinesin motility assays, whereas single-isotype α1β3 GDP-tubulin lattices are stabilised but not expanded. This isotype-specific action of taxol drives gliding of segmented-isotype GDP-taxol microtubules along convoluted, sinusoidal paths, because their expanded α1β4 segments try to glide faster than their compacted α1β3 segments. In GMPCPP, single-isotype α1β3 and α1β4 lattices both show accelerated gliding, indicating that both can in principle be driven to expand. We therefore propose that taxol-induced lattice expansion requires a higher taxol occupancy than taxol-induced stabilisation, and that higher taxol occupancies are accessible to α1β4 but not α1β3 single-isotype lattices.
Item Type: | Journal Article | |||||||||
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Subjects: | Q Science > Q Science (General) Q Science > QH Natural history > QH301 Biology Q Science > QP Physiology R Medicine > RC Internal medicine |
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Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences > Cell & Developmental Biology Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School |
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Library of Congress Subject Headings (LCSH): | Paclitaxel, Tubulins, Microtubules, Kinesin , Biophysics | |||||||||
Journal or Publication Title: | Communications Biology | |||||||||
Publisher: | Springer Nature | |||||||||
Official Date: | 16 September 2023 | |||||||||
Dates: |
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Volume: | 6 | |||||||||
Article Number: | 946 | |||||||||
DOI: | 10.1038/s42003-023-05306-y | | |||||||||
Status: | Peer Reviewed | |||||||||
Publication Status: | Published | |||||||||
Access rights to Published version: | Open Access (Creative Commons) | |||||||||
Date of first compliant deposit: | 22 September 2023 | |||||||||
Date of first compliant Open Access: | 25 September 2023 | |||||||||
Grant number: | 220387/Z/20/Z | |||||||||
RIOXX Funder/Project Grant: |
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Open Access Version: |
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