Dynamic microtubule-end structure governs multivalent kinetochore coupling by the Dam1c ring
- 1Birkbeck, University of London
Abstract
Accurate chromosome segregation relies on kinetochores maintaining load-bearing attachments to dynamic microtubule ends, a coupling in which the Dam1 complex ring is central. How the microtubule-end structure and ring-microtubule interactions collectively determine attachment stability and drive force transduction remains unresolved. Here, we use multiscale modeling to show that the ring forms a "fuzzy" complex mediated by a dynamic network of intrinsically disordered regions, enabling both high-affinity binding and free diffusion along the microtubule lattice. Crucially, we find that this prototypic disordered-disordered protein complex provides most of the kinetochore-microtubule stabilization. By contrast, protofilament bending, commonly thought to drive force transduction, is sensitive to the arrangement of protofilaments along the ring and insufficient on its own to establish a robust coupling. The architecture of the dynamic microtubule end unifies these mechanisms by controlling both the progressive loss of fuzzy contacts and the resistance generated by protofilament bending. By accounting for the full conformational ensemble of microtubule structures, our model produces rupture forces similar to those previously measured and explains the distinct, tension-dependent behavior of kinetochore attachments to growing versus shortening microtubule ends. We propose that the Dam1 complex ring acts as a biased-diffusion coupler that probes and gradually remodels the evolving conformational landscape of the microtubule end under tension.
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BibTeX
@misc{kalutskii2026dynamic,
title = {{Dynamic microtubule-end structure governs multivalent kinetochore coupling by the Dam1c ring}},
author = {M. Kalutskii and H. Grubmueller and M. Igaev},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.17.752406},
url = {https://www.biorxiv.org/content/10.64898/2026.09.17.752406v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Dynamic microtubule-end structure governs multivalent kinetochore coupling by the Dam1c ring
AU - M. Kalutskii
AU - H. Grubmueller
AU - M. Igaev
PY - 2026
DA - 2026/09/17
PB - bioRxiv
DO - 10.64898/2026.09.17.752406
UR - https://www.biorxiv.org/content/10.64898/2026.09.17.752406v1
AB - Accurate chromosome segregation relies on kinetochores maintaining load-bearing attachments to dynamic microtubule ends, a coupling in which the Dam1 complex ring is central. How the microtubule-end structure and ring-microtubule interactions collectively determine attachment stability and drive force transduction remains unresolved. Here, we use multiscale modeling to show that the ring forms a "fuzzy" complex mediated by a dynamic network of intrinsically disordered regions, enabling both high-affinity binding and free diffusion along the microtubule lattice. Crucially, we find that this prototypic disordered-disordered protein complex provides most of the kinetochore-microtubule stabilization. By contrast, protofilament bending, commonly thought to drive force transduction, is sensitive to the arrangement of protofilaments along the ring and insufficient on its own to establish a robust coupling. The architecture of the dynamic microtubule end unifies these mechanisms by controlling both the progressive loss of fuzzy contacts and the resistance generated by protofilament bending. By accounting for the full conformational ensemble of microtubule structures, our model produces rupture forces similar to those previously measured and explains the distinct, tension-dependent behavior of kinetochore attachments to growing versus shortening microtubule ends. We propose that the Dam1 complex ring acts as a biased-diffusion coupler that probes and gradually remodels the evolving conformational landscape of the microtubule end under tension.
ER -