Structure of the RZZ complex and molecular basis of Spindly-driven corona assembly at human kinetochores.
EMBO J
; 41(9): e110411, 2022 05 02.
Article
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| MEDLINE
| ID: mdl-35373361
ABSTRACT
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.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Cinetocoros
/
Huso Acromático
Límite:
Animals
/
Humans
Idioma:
En
Año:
2022
Tipo del documento:
Article