The structure of purified kinetochores reveals multiple microtubule-attachment sites

Abstract

Chromosomes must be accurately partitioned to daughter cells to prevent aneuploidy, a hallmark of many tumors and birth defects. Kinetochores are the macromolecular machines that segregate chromosomes by maintaining load-bearing attachments to the dynamic tips of microtubules. Here, we present the structure of isolated budding yeast kinetochore particles as visualized by electron microscopy (EM) and electron tomography of negatively stained preparations. The kinetochore appears as a ~126 nm particle containing a large central hub surrounded by multiple outer globular domains. In the presence of microtubules, some particles also have a ring that encircles the microtubule. Our data show that kinetochores bind to microtubules via multivalent attachments and lay the foundation to uncover the key mechanical and regulatory mechanisms by which kinetochores control chromosome segregation and cell division.