title: Structure of the MIND Complex Defines a Regulatory Focus for Yeast Kinetochore Assembly.
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.
authors.affiliation: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 250 Longwood Avenue, Boston, MA 02115, USA.
authors.forename: Yoana N
authors.initials: YN
authors.lastname: Dimitrova
authors.affiliation: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 250 Longwood Avenue, Boston, MA 02115, USA.
authors.forename: Simon
authors.initials: S
authors.lastname: Jenni
authors.affiliation: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 250 Longwood Avenue, Boston, MA 02115, USA.
authors.forename: Roberto
authors.initials: R
authors.lastname: Valverde
authors.affiliation: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 250 Longwood Avenue, Boston, MA 02115, USA.
authors.forename: Yadana
authors.initials: Y
authors.lastname: Khin
authors.affiliation: 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.
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Harrison
mesh_terms: D002868:Chromosomal Proteins, Non-Histone / Q000737:chemistry* / Q000378:metabolism; D018360:Crystallography, X-Ray; D005656:Fungal Proteins / Q000737:chemistry* / Q000378:metabolism; D018386:Kinetochores / Q000737:chemistry* / Q000378:metabolism; D007716:Kluyveromyces / Q000737:chemistry* / Q000166:cytology / Q000378:metabolism; D046912:Multiprotein Complexes / Q000737:chemistry* / Q000378:metabolism
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D005656:Fungal Proteins; D046912:Multiprotein Complexes
keywords: CENP-C; Ctf19 complex; Ipl1/AuroraB phosphoregulation; Mif2; Mis12; Ndc80 complex; cell division; kinetochore structure; point-centromere yeast; x-ray crystallography