CENP‐T provides a structural platform for outer kinetochore assembly. (18th January 2013)

• Record Type: Journal Article
• Authors: Nishino, Tatsuya; Rago, Florencia; Hori, Tetsuya; Tomii, Kentaro; Cheeseman, Iain M; Fukagawa, Tatsuo
• Is Part Of: EMBO journal. Volume 32:Number 3(2013)
• Page Start: 424
• Page End: 436
• Publication Date: 2013-01-18
• Subjects: Molecular biology -- Periodicals; 572.805
• DOI: 10.1038/emboj.2012.348
• Languages: English
• ISSNs: 0261-4189

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>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.</p> </abstract>