CENP‐T provides a structural platform for outer kinetochore assembly |
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| Authors: | Tatsuya Nishino Florencia Rago Tetsuya Hori Kentaro Tomii Iain M Cheeseman Tatsuo Fukagawa |
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| Affiliation: | 1. Department of Molecular Genetics, National Institute of Genetics and The Graduate University for Advanced Studies (SOKENDAI), , Shizuoka, Japan;2. Whitehead Institute for Biomedical Research and Department of Biology, Massachusetts Institute of Technology, , Cambridge, MA, USA;3. Computational Biology Research Center, National Institute of Advanced Industrial Science and Technology, , Tokyo, Japan |
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| Abstract: | The kinetochore forms a dynamic interface with microtubules from the mitotic spindle during mitosis. The Ndc80 complex acts as the key microtubule‐binding complex at kinetochores. However, it is unclear how the Ndc80 complex associates with the inner kinetochore proteins that assemble upon centromeric chromatin. Here, based on a high‐resolution structural analysis, we demonstrate that the N‐terminal region of vertebrate CENP‐T interacts with the ‘RWD' domain in the Spc24/25 portion of the Ndc80 complex. Phosphorylation of CENP‐T strengthens a cryptic hydrophobic interaction between CENP‐T and Spc25 resulting in a phospho‐regulated interaction that occurs without direct recognition of the phosphorylated residue. The Ndc80 complex interacts with both CENP‐T and the Mis12 complex, but we find that these interactions are mutually exclusive, supporting a model in which two distinct pathways target the Ndc80 complex to kinetochores. Our results provide a model for how the multiple protein complexes at kinetochores associate in a phospho‐regulated manner. |
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| Keywords: | CENP‐T kinetochore mitosis Spc24/25 X‐ray structure |
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