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Structure of the RZZ complex and molecular basis of Spindly-driven corona assembly at human kinetochores

Tobias Raisch, Giuseppe Ciossani, Ennio d’Amico, Verena Cmentowski, Sara Carmignani, View ORCID ProfileStefano Maffini, Felipe Merino, Sabine Wohlgemuth, Ingrid R. Vetter, View ORCID ProfileStefan Raunser, Andrea Musacchio
doi: https://doi.org/10.1101/2021.12.03.471119
Tobias Raisch
1Department of Structural Biochemistry, Max Planck Institute of Molecular Physiology, Otto-Hahn Straße 11, 44227 Dortmund, Germany
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Giuseppe Ciossani
2Department of Mechanistic Cell Biology, Max Planck Institute of Molecular Physiology, Otto-Hahn Straße 11, 44227 Dortmund, Germany
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Ennio d’Amico
2Department of Mechanistic Cell Biology, Max Planck Institute of Molecular Physiology, Otto-Hahn Straße 11, 44227 Dortmund, Germany
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Verena Cmentowski
2Department of Mechanistic Cell Biology, Max Planck Institute of Molecular Physiology, Otto-Hahn Straße 11, 44227 Dortmund, Germany
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Sara Carmignani
2Department of Mechanistic Cell Biology, Max Planck Institute of Molecular Physiology, Otto-Hahn Straße 11, 44227 Dortmund, Germany
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Stefano Maffini
2Department of Mechanistic Cell Biology, Max Planck Institute of Molecular Physiology, Otto-Hahn Straße 11, 44227 Dortmund, Germany
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  • ORCID record for Stefano Maffini
Felipe Merino
1Department of Structural Biochemistry, Max Planck Institute of Molecular Physiology, Otto-Hahn Straße 11, 44227 Dortmund, Germany
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Sabine Wohlgemuth
2Department of Mechanistic Cell Biology, Max Planck Institute of Molecular Physiology, Otto-Hahn Straße 11, 44227 Dortmund, Germany
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Ingrid R. Vetter
2Department of Mechanistic Cell Biology, Max Planck Institute of Molecular Physiology, Otto-Hahn Straße 11, 44227 Dortmund, Germany
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Stefan Raunser
1Department of Structural Biochemistry, Max Planck Institute of Molecular Physiology, Otto-Hahn Straße 11, 44227 Dortmund, Germany
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  • ORCID record for Stefan Raunser
Andrea Musacchio
2Department of Mechanistic Cell Biology, Max Planck Institute of Molecular Physiology, Otto-Hahn Straße 11, 44227 Dortmund, Germany
3Centre for Medical Biotechnology, Faculty of Biology, University Duisburg-Essen, Essen, Germany
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  • For correspondence: andrea.musacchio@mpi-dortmund.mpg.de stefan.raunser@mpi-dortmund.mpg.de ingrid.vetter@mpi-dortmund.mpg.de
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Abstract

In metazoans, a ≍1 megadalton (MDa) super-complex comprising the Dynein-Dynactin adaptor Spindly and the ROD-Zwilch-ZW10 (RZZ) complex is the building block of a fibrous biopolymer, the kinetochore fibrous corona. The corona assembles on mitotic kinetochores to promote microtubule capture and spindle assembly checkpoint (SAC) signaling. We report here a high-resolution cryo-EM structure that captures the essential features of the RZZ complex, including a farnesyl binding site required for Spindly binding. Using a highly predictive in vitro assay, we demonstrate that the SAC kinase MPS1 is necessary and sufficient for corona assembly at supercritical concentrations of the RZZ-Spindly (RZZS) complex, and describe the molecular mechanism of phosphorylation-dependent filament nucleation. We identify several structural requirements for RZZS polymerization in rings and sheets. Finally, we identify determinants of kinetochore localization and corona assembly of Spindly. Our results describe a framework for the long-sought-for molecular basis of corona assembly on metazoan kinetochores.

Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license.
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Posted December 06, 2021.
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Structure of the RZZ complex and molecular basis of Spindly-driven corona assembly at human kinetochores
Tobias Raisch, Giuseppe Ciossani, Ennio d’Amico, Verena Cmentowski, Sara Carmignani, Stefano Maffini, Felipe Merino, Sabine Wohlgemuth, Ingrid R. Vetter, Stefan Raunser, Andrea Musacchio
bioRxiv 2021.12.03.471119; doi: https://doi.org/10.1101/2021.12.03.471119
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Structure of the RZZ complex and molecular basis of Spindly-driven corona assembly at human kinetochores
Tobias Raisch, Giuseppe Ciossani, Ennio d’Amico, Verena Cmentowski, Sara Carmignani, Stefano Maffini, Felipe Merino, Sabine Wohlgemuth, Ingrid R. Vetter, Stefan Raunser, Andrea Musacchio
bioRxiv 2021.12.03.471119; doi: https://doi.org/10.1101/2021.12.03.471119

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