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| Title | Assembly and phosphoregulatory mechanisms of the budding yeast outer kinetochore KMN complex. |
|---|---|
| Journal, issue, pages | J Cell Biol, Vol. 225, Issue 5, Year 2026 |
| Publish date | May 4, 2026 |
Authors | Noah N Turner / Ziguo Zhang / Jing Yang / Kyle W Muir / Stephen H McLaughlin / Tomos Morgan / David Barford / ![]() |
| PubMed Abstract | During mitosis and meiosis, kinetochores mediate interactions between chromosomes and spindle microtubules. Kinetochores are multi-megadalton protein complexes essential for chromosome segregation; ...During mitosis and meiosis, kinetochores mediate interactions between chromosomes and spindle microtubules. Kinetochores are multi-megadalton protein complexes essential for chromosome segregation; however, recent structural, functional, and evolutionary studies have revealed divergent mechanisms of kinetochore assembly. Here, we use cryo-EM to understand the structural mechanisms by which the budding yeast microtubule-binding outer kinetochore KMN complex assembles, and how its interactions with the centromere-binding inner kinetochore are regulated. The KMN complex comprises three subcomplexes: Knl1c, Mis12cMtw1c, and Ndc80c. We show how C-terminal motifs of the Mis12cMtw1c subunits Dsn1, Mis12Mtw1, and Nnf1 bind Knl1c and Ndc80c. At the opposite end of the Mis12cMtw1c stalk, an N-terminal auto-inhibitory segment of Dsn1 (Dsn1AI) folds into two α-helices that engage the Mis12cMtw1c head 1 domain, thereby occluding binding sites for the inner kinetochore subunits CENP-CMif2 and CENP-UAme1, reducing their affinity for Mis12cMtw1. Our structure reveals how Aurora BIpl1 phosphorylation of Dsn1AI would release this auto-inhibition to substantially strengthen preexisting connections between the inner and outer kinetochore. |
External links | J Cell Biol / PubMed:41956986 / PubMed Central |
| Methods | EM (single particle) |
| Resolution | 4.8 - 7.2 Å |
| Structure data | ![]() EMDB-54576: Consensus cryo-EM map of the Saccharomyces cerevisiae KMN junction complex lacking the Mis12c(Mtw1c) head 2 domain ![]() EMDB-54577: Mutlbody refinement cryo-EM density map of the base of the Saccharomyces cerevisiae KMN junction complex ![]() EMDB-54578: Multibody refinement cryo-EM density map of the apex of the Saccharomyces cerevisiae KMN junction complex EMDB-54579: Composite cryo-EM density map of the Saccharomyces cerevisiae KMN junction complex lacking the Mis12c(Mtw1c) head 2 domain EMDB-54586: Multibody refinement cryo-EM density map of the base of the Saccharomyces cerevisiae KMN junction complex with Mis12c(Mtw1c) head 2 domain resolved EMDB-54602, PDB-9s5n: |
| Source |
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Keywords | CELL CYCLE / Kinetochore / chromosome segregation / mitosis |
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