Structural mechanism of outer kinetochore Dam1-Ndc80 complex assembly on microtubules

• 成果类型: Article
• 署名作者: Muir, Kyle W.; Batters, Christopher; Dendooven, Tom; Yang, Jing; Zhang, Ziguo; Burt, Alister; Barford, David
• 署名单位: MRC Laboratory Molecular Biology
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-10629
• DOI: 10.1126/science.adj8736
• 发表日期: 2023-12-08
• 页码: 1184-1190
• 关键词: error-correction; bi-orientation; dam1 complex; ring complex; dash complex; spindle; tension; protein; architecture; driven

摘要

Kinetochores couple chromosomes to the mitotic spindle to segregate the genome during cell division. An error correction mechanism drives the turnover of kinetochore-microtubule attachments until biorientation is achieved. The structural basis for how kinetochore-mediated chromosome segregation is accomplished and regulated remains an outstanding question. In this work, we describe the cryo-electron microscopy structure of the budding yeast outer kinetochore Ndc80 and Dam1 ring complexes assembled onto microtubules. Complex assembly occurs through multiple interfaces, and a staple within Dam1 aids ring assembly. Perturbation of key interfaces suppresses yeast viability. Force-rupture assays indicated that this is a consequence of impaired kinetochoremicrotubule attachment. The presence of error correction phosphorylation sites at Ndc80-Dam1 ring complex interfaces and the Dam1 staple explains how kinetochore-microtubule attachments are destabilized and reset.