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Cell. 2016 Nov 3;167(4):1014-1027.e12. doi: 10.1016/j.cell.2016.10.011. Epub 2016 Oct 27.

Structure of the MIND Complex Defines a Regulatory Focus for Yeast Kinetochore Assembly.

Author information

1
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 250 Longwood Avenue, Boston, MA 02115, USA.
2
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 250 Longwood Avenue, Boston, MA 02115, USA; Howard Hughes Medical Institute, 250 Longwood Avenue, Boston, MA 02115, USA. Electronic address: harrison@crystal.harvard.edu.

Abstract

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:

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

PMID:
27881300
PMCID:
PMC5856483
DOI:
10.1016/j.cell.2016.10.011
[Indexed for MEDLINE]
Free PMC Article

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