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Journal Article

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

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Raisch, T., Ciossani, G., d'Amico, E., Cmentowski, V., Carmignani, S., Maffini, S., et al. (2022). Structure of the RZZ complex and molecular basis of Spindly-driven corona assembly at human kinetochores. The EMBO Journal, 41(9): e110411. doi:10.15252/embj.2021110411.

Cite as: https://hdl.handle.net/21.11116/0000-000B-A9DA-1
In metazoans, a ≈1 megadalton (MDa) multiprotein 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.