7qpg

Publication Abstract from PubMed

In metazoans, a approximately 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.

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 EMBO J. 2022 May 2;41(9):e110411. doi: 10.15252/embj.2021110411. Epub 2022 Apr 4. PMID:35373361^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.