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

doi:10.15252/embj.2021110411

Datensatz

DATENSATZ AKTIONENEXPORT

Zur Ablage hinzufügen

Lokale TagsFreigabegeschichteDetailsÜbersicht

Freigegeben

Zeitschriftenartikel

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

MPG-Autoren

Es sind keine MPG-Autoren in der Publikation vorhanden

Externe Ressourcen

Es sind keine externen Ressourcen hinterlegt

Volltexte (beschränkter Zugriff)

Für Ihren IP-Bereich sind aktuell keine Volltexte freigegeben.

Volltexte (frei zugänglich)

Es sind keine frei zugänglichen Volltexte in PuRe verfügbar

Ergänzendes Material (frei zugänglich)

Es sind keine frei zugänglichen Ergänzenden Materialien verfügbar

Zitation

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.

Zitierlink: https://hdl.handle.net/21.11116/0000-000B-A9DA-1

Zusammenfassung

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.