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Stable kinetochore-microtubule attachment requires loop-dependent Ndc80-Ndc80 binding
Open accessPreprint — published as 10.15252/embj.2022112504 · Paper page
Abstract
During cell division, kinetochores link chromosomes to spindle microtubules. The Ndc80 complex, a crucial microtubule binder, populates each kinetochore with dozens of copies. Whether adjacent Ndc80 complexes cooperate to promote microtubule binding remains unclear. Here we demonstrate that the Ndc80 loop, a short sequence identified across eukaryotes and predicted to interrupt the Ndc80 coiled-coil, promotes direct interactions between full-length Ndc80 complexes. Both in dividing cells and in a fully reconstituted system, these interactions are essential for the formation of force-resistant kinetochore-microtubule attachments, explaining why deletion of the loop ablates chromosome congression. The loop may fold into a more rigid structure than previously assumed and we identify point mutations that impair Ndc80-Ndc80 interactions and recapitulate the effects of loop depletion. The loop also promotes spindle checkpoint signaling, suggesting that the organisation of adjacent Ndc80 complexes is crucial to couple kinetochore-microtubule binding to cell cycle control.
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Jumper, J., Evans, R., Pritzel, A., Green, T., Figurnov, M., Ronneberger, O., Tunyasuvunakool, K., Bates, R., Žídek, A., Potapenko, A., et al. (2021) · Nature · doi:10.1038/s41586-021-03819-2 · Cited by 43,764
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Metadata
- Authors
- Polley, S., Müschenborn, H., Terbeck, M., De Antoni, A., Vetter, I. R., Dogterom, M., Musacchio, A., Volkov, V. A., & Huis in ‘t Veld, P. J.
- Affiliations
- Max Planck Institute of Molecular Physiology (DE)
- Delft University of Technology (NL)
- Queen Mary University of London (GB)
- Corresponding author
- Musacchio, Andrea
- Volkov, Vladimir A.
- ORCID
- Venue
- The EMBO Journal
- Publisher
- openRxiv
- Published
- 2022-08-26
- Volume
- 42
- Issue
- 13
- Pages
- e112504-e112504
- ISSN
- 0261-4189 (ISSN-L)
- PMC
- PMC10308368
- OpenAlex
- W4377094368
- Cited by
- 30
- References
- 1
- Citations by year
- 2026: 8 · 2025: 6 · 2024: 8 · 2023: 8
- FWCI
- 4.32
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc-nd
- Locations
- The EMBO Journal (publishedVersion, cc-by-nc-nd)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion, cc-by-nc-nd)
- Queen Mary Research Online (Queen Mary University of London) (submittedVersion, cc-by-nc-nd)
- Research Repository (Delft University of Technology) (submittedVersion)
- Funders
- Queen Mary, University of London
- European Research Council
- H2020 European Research Council (951430)
- FP7 Ideas: European Research Council (609822)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Keywords
- Ndc80 complex, kinetochore-microtubule attachment, coiled coil, microtubule binding, spindle assembly checkpoint, mitotic arrest, chromosome segregation, mitosis
- MeSH terms
- Animals, Microtubule-Associated Proteins, Microtubules, Mitosis, Protein Binding, Kinetochores, Chromosome Segregation
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