Cell
Volume 167, Issue 4, 3 November 2016, Pages 1014-1027.e12
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Article
Structure of the MIND Complex Defines a Regulatory Focus for Yeast Kinetochore Assembly

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Highlights

  • MIND-complex crystal structure defines pivotal interactions in kinetochore assembly

  • One end of 200-Å-long MIND rod binds Mif2 and COMA; the other, Ndc80 complex

  • Phosphorylation of Dsn1 subunit relieves autoinhibition of Mif2 and COMA binding

Summary

Kinetochores connect centromeric nucleosomes with mitotic-spindle microtubules through conserved, cross-interacting protein subassemblies. In budding yeast, the heterotetrameric MIND complex (Mtw1, Nnf1, Nsl1, Dsn1), ortholog of the metazoan Mis12 complex, joins the centromere-proximal components, Mif2 and COMA, with the principal microtubule-binding component, the Ndc80 complex (Ndc80C). We report the crystal structure of Kluyveromyces lactis MIND and examine its partner interactions, to understand the connection from a centromeric nucleosome to a much larger microtubule. MIND resembles an elongated, asymmetric Y; two globular heads project from a coiled-coil shaft. An N-terminal extension of Dsn1 from one head regulates interactions of the other head, blocking binding of Mif2 and COMA. Dsn1 phosphorylation by Ipl1/Aurora B relieves this autoinhibition, enabling MIND to join an assembling kinetochore. A C-terminal extension of Dsn1 recruits Ndc80C to the opposite end of the shaft. The structure and properties of MIND show how it integrates phospho-regulatory inputs for kinetochore assembly and disassembly.

Keywords

cell division
Mis12
kinetochore structure
Ipl1/AuroraB phosphoregulation
Ndc80 complex
Mif2
CENP-C
Ctf19 complex
x-ray crystallography
point-centromere yeast

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