| Structural highlights
Function
[SPC25_YEAST] Acts as a component of the essential kinetochore-associated NDC80 complex, which is involved in chromosome segregation and spindle checkpoint activity.[1] [2] [SPC24_YEAST] Acts as a component of the essential kinetochore-associated NDC80 complex, which is involved in chromosome segregation and spindle checkpoint activity.[3] [4] [5]
Publication Abstract from PubMed
The Ndc80 complex is the key microtubule-binding element of the kinetochore. In contrast to the well-characterized interaction of Ndc80-Nuf2 heads with microtubules, little is known about how the Spc24-25 heterodimer connects to centromeric chromatin. Here, we present molecular details of Spc24-25 in complex with the histone-fold protein Cnn1/CENP-T illustrating how this connection ultimately links microtubules to chromosomes. The conserved Ndc80 receptor motif of Cnn1 is bound as an alpha helix in a hydrophobic cleft at the interface between Spc24 and Spc25. Point mutations that disrupt the Ndc80-Cnn1 interaction also abrogate binding to the Mtw1 complex and are lethal in yeast. We identify a Cnn1-related motif in the Dsn1 subunit of the Mtw1 complex, necessary for Ndc80 binding and essential for yeast growth. Replacing this region with the Cnn1 peptide restores viability demonstrating functionality of the Ndc80-binding module in different molecular contexts. Finally, phosphorylation of the Cnn1 N-terminus coordinates the binding of the two competing Ndc80 interaction partners. Together, our data provide structural insights into the modular binding mechanism of the Ndc80 complex to its centromere recruiters.
A structural basis for kinetochore recruitment of the Ndc80 complex via two distinct centromere receptors.,Malvezzi F, Litos G, Schleiffer A, Heuck A, Mechtler K, Clausen T, Westermann S EMBO J. 2013 Feb 6;32(3):409-23. doi: 10.1038/emboj.2012.356. Epub 2013 Jan 18. PMID:23334295[6]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ Malvezzi F, Litos G, Schleiffer A, Heuck A, Mechtler K, Clausen T, Westermann S. A structural basis for kinetochore recruitment of the Ndc80 complex via two distinct centromere receptors. EMBO J. 2013 Feb 6;32(3):409-23. doi: 10.1038/emboj.2012.356. Epub 2013 Jan 18. PMID:23334295 doi:http://dx.doi.org/10.1038/emboj.2012.356
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