Structure of the RZZ complex and molecular basis of Spindly-driven corona assembly at human kinetochores
Raisch T, Ciossani G, d'Amico E, Cmentowski V, Carmignani S, Maffini S, Merino F, Wohlgemuth S, Vetter IR, Raunser S, Musacchio A (2022). EMBO J
The corona assembles on mitotic kinetochores to promote microtubule capture and spindle assembly checkpoint (SAC) signaling. The groups of Andrea Musacchio and Stefan Raunser have now revealed a high-resolution cryo-EM structure that captures the essential features of its main building block, the RZZ complex, including a farnesyl-binding site required for Spindly binding. Using a highly predictive in vitro assay, the scientists 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. They identify several structural requirements for RZZS polymerization in rings and sheets and determinants of kinetochore localization and corona assembly of Spindly. The results describe a framework for the long-sought-for molecular basis of corona assembly on metazoan kinetochores.
