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TitleStructure of the RZZ complex and molecular basis of Spindly-driven corona assembly at human kinetochores.
Journal, issue, pagesEMBO J, Vol. 41, Issue 9, Page e110411, Year 2022
Publish dateApr 4, 2022
AuthorsTobias Raisch / Giuseppe Ciossani / Ennio d'Amico / Verena Cmentowski / Sara Carmignani / Stefano Maffini / Felipe Merino / Sabine Wohlgemuth / Ingrid R Vetter / Stefan Raunser / Andrea Musacchio /
PubMed AbstractIn 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 ...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.
External linksEMBO J / PubMed:35373361 / PubMed Central
MethodsEM (single particle)
Resolution3.9 Å
Structure data

14120

7qpg

EMDB-14120, PDB-7qpg:
Human RZZ kinetochore corona complex.
Method: EM (single particle) / Resolution: 3.9 Å

Source
  • homo sapiens (human)
KeywordsCELL CYCLE / Kinetochore / centromere / chromosome segregation / mitosis

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