5t6j

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Structure of the MIND Complex Shows a Regulatory Focus of Yeast Kinetochore AssemblyStructure of the MIND Complex Shows a Regulatory Focus of Yeast Kinetochore Assembly

Structural highlights

5t6j is a 3 chain structure with sequence from Baker's yeast. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Gene:SPC24, YMR117C, YM9718.16C (Baker's yeast), SPC25, YER018C (Baker's yeast), DSN1, YIR010W, YIB10W (Baker's yeast)
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[SPC24_YEAST] Acts as a component of the essential kinetochore-associated NDC80 complex, which is involved in chromosome segregation and spindle checkpoint activity.[1] [2] [3] [DSN1_YEAST] Acts as essential component of the kinetochore MIND complex, which is required for the spindle checkpoint and kinetochore integrity. MIND plays a role in establishing a bipolar spindle-kinetochore interaction by joining kinetochore subunits contacting DNA to those contacting microtubules.[4] [5] [SPC25_YEAST] Acts as a component of the essential kinetochore-associated NDC80 complex, which is involved in chromosome segregation and spindle checkpoint activity.[6] [7]

Publication Abstract from PubMed

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.

Structure of the MIND Complex Defines a Regulatory Focus for Yeast Kinetochore Assembly.,Dimitrova YN, Jenni S, Valverde R, Khin Y, Harrison SC Cell. 2016 Nov 3;167(4):1014-1027.e12. doi: 10.1016/j.cell.2016.10.011. Epub 2016, Oct 27. PMID:27881300[8]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

  1. ↑ Wigge PA, Kilmartin JV. The Ndc80p complex from Saccharomyces cerevisiae contains conserved centromere components and has a function in chromosome segregation. J Cell Biol. 2001 Jan 22;152(2):349-60. PMID:11266451
  2. ↑ Le Masson I, Saveanu C, Chevalier A, Namane A, Gobin R, Fromont-Racine M, Jacquier A, Mann C. Spc24 interacts with Mps2 and is required for chromosome segregation, but is not implicated in spindle pole body duplication. Mol Microbiol. 2002 Mar;43(6):1431-43. PMID:11952896
  3. ↑ McCleland ML, Gardner RD, Kallio MJ, Daum JR, Gorbsky GJ, Burke DJ, Stukenberg PT. The highly conserved Ndc80 complex is required for kinetochore assembly, chromosome congression, and spindle checkpoint activity. Genes Dev. 2003 Jan 1;17(1):101-14. PMID:12514103 doi:http://dx.doi.org/10.1101/gad.1040903
  4. ↑ Euskirchen GM. Nnf1p, Dsn1p, Mtw1p, and Nsl1p: a new group of proteins important for chromosome segregation in Saccharomyces cerevisiae. Eukaryot Cell. 2002 Apr;1(2):229-40. PMID:12455957
  5. ↑ De Wulf P, McAinsh AD, Sorger PK. Hierarchical assembly of the budding yeast kinetochore from multiple subcomplexes. Genes Dev. 2003 Dec 1;17(23):2902-21. Epub 2003 Nov 21. PMID:14633972 doi:http://dx.doi.org/10.1101/gad.1144403
  6. ↑ Wigge PA, Kilmartin JV. The Ndc80p complex from Saccharomyces cerevisiae contains conserved centromere components and has a function in chromosome segregation. J Cell Biol. 2001 Jan 22;152(2):349-60. PMID:11266451
  7. ↑ McCleland ML, Gardner RD, Kallio MJ, Daum JR, Gorbsky GJ, Burke DJ, Stukenberg PT. The highly conserved Ndc80 complex is required for kinetochore assembly, chromosome congression, and spindle checkpoint activity. Genes Dev. 2003 Jan 1;17(1):101-14. PMID:12514103 doi:http://dx.doi.org/10.1101/gad.1040903
  8. ↑ Dimitrova YN, Jenni S, Valverde R, Khin Y, Harrison SC. Structure of the MIND Complex Defines a Regulatory Focus for Yeast Kinetochore Assembly. Cell. 2016 Nov 3;167(4):1014-1027.e12. doi: 10.1016/j.cell.2016.10.011. Epub 2016, Oct 27. PMID:27881300 doi:http://dx.doi.org/10.1016/j.cell.2016.10.011

5t6j, resolution 1.75Å

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