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Cryo-EM structure (4.5-Å) of yeast Kinesin-5–microtubule complex reveals a distinct binding footprint and mechanism of drug resistance
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von Loeffelholz, Ottilie, Peña, Alejandro, Drummond, Douglas R., Cross, R. A. and Moores, Carolyn Ann (2019) Cryo-EM structure (4.5-Å) of yeast Kinesin-5–microtubule complex reveals a distinct binding footprint and mechanism of drug resistance. Journal of Molecular Biology, 431 (4). pp. 864-872. doi:10.1016/j.jmb.2019.01.011 ISSN 0022-2836.
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WRAP-Cryo-EM-structure-(4.5-Å)-yeast-Kinesin-5–microtubule-complex-Cross-2019.pdf - Published Version - Requires a PDF viewer. Available under License Creative Commons Attribution 4.0. Download (1905Kb) | Preview |
Official URL: http://dx.doi.org/10.1016/j.jmb.2019.01.011
Abstract
Kinesin-5s are microtubule-dependent motors that drive spindle pole separation during mitosis. We used cryo-electron microscopy to determine the 4.5-Å resolution structure of the motor domain of the fission yeast kinesin-5 Cut7 bound to fission yeast microtubules and explored the topology of the motor–microtubule interface and the susceptibility of the complex to drug binding. Despite their non-canonical architecture and mechanochemistry, Schizosaccharomyces pombe microtubules were stabilized by epothilone at the taxane binding pocket. The overall Cut7 footprint on the S. pombe microtubule surface is altered compared to mammalian tubulin microtubules because of their different polymer architectures. However, the core motor–microtubule interaction is tightly conserved, reflected in similar Cut7 ATPase activities on each microtubule type. AMPPNP-bound Cut7 adopts a kinesin-conserved ATP-like conformation including cover neck bundle formation. However, the Cut7 ATPase is not blocked by a mammalian-specific kinesin-5 inhibitor, consistent with the non-conserved sequence and structure of its loop5 insertion.
| Item Type: | Journal Article | ||||||||||||||||||
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| Subjects: | Q Science > QH Natural history Q Science > QP Physiology |
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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 > Biomedical Sciences Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School |
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| Library of Congress Subject Headings (LCSH): | Kinesin, Microtubules, Mitosis, Spindle (Cell division), Tubulins, Schizosaccharomyces pombe | ||||||||||||||||||
| Journal or Publication Title: | Journal of Molecular Biology | ||||||||||||||||||
| Publisher: | Academic Press | ||||||||||||||||||
| ISSN: | 0022-2836 | ||||||||||||||||||
| Official Date: | 15 February 2019 | ||||||||||||||||||
| Dates: |
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| Volume: | 431 | ||||||||||||||||||
| Number: | 4 | ||||||||||||||||||
| Page Range: | pp. 864-872 | ||||||||||||||||||
| DOI: | 10.1016/j.jmb.2019.01.011 | ||||||||||||||||||
| Status: | Peer Reviewed | ||||||||||||||||||
| Publication Status: | Published | ||||||||||||||||||
| Access rights to Published version: | Open Access (Creative Commons) | ||||||||||||||||||
| Date of first compliant deposit: | 12 February 2019 | ||||||||||||||||||
| Date of first compliant Open Access: | 13 February 2019 | ||||||||||||||||||
| RIOXX Funder/Project Grant: |
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