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

Publication Type:

Journal Article


Cell, Volume 167, Issue 4, p.1014-1027.e12 (2016)


Chromosomal Proteins, Non-Histone, Crystallography, X-Ray, Fungal Proteins, Kinetochores, Kluyveromyces, Multiprotein Complexes


<p>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.</p>

5T58 (MIND-C1), 5T51 (MN-C2), 5T59 (MN-C2-Mif21-41), 5T6J (Spc24/Spc25-Dsn1560-572)