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-Structure paper
タイトル | Structure of the RZZ complex and molecular basis of Spindly-driven corona assembly at human kinetochores. |
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ジャーナル・号・ページ | EMBO J, Vol. 41, Issue 9, Page e110411, Year 2022 |
掲載日 | 2022年4月4日 |
著者 | Tobias Raisch / Giuseppe Ciossani / Ennio d'Amico / Verena Cmentowski / Sara Carmignani / Stefano Maffini / Felipe Merino / Sabine Wohlgemuth / Ingrid R Vetter / Stefan Raunser / Andrea Musacchio / |
PubMed 要旨 | 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 ...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. |
リンク | EMBO J / PubMed:35373361 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 3.9 Å |
構造データ | EMDB-14120, PDB-7qpg: |
由来 |
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キーワード | CELL CYCLE (細胞周期) / Kinetochore (動原体) / centromere (セントロメア) / chromosome segregation / mitosis (有糸分裂) |