| Structural highlights
Function
NDC80_HUMAN Acts as a component of the essential kinetochore-associated NDC80 complex, which is required for chromosome segregation and spindle checkpoint activity. Required for kinetochore integrity and the organization of stable microtubule binding sites in the outer plate of the kinetochore.[1] [2] [3] [4] [5] [6] [7] [8] [9]
Publication Abstract from PubMed
The conserved Ndc80 kinetochore complex, Ndc80c, is the principal link between mitotic spindle microtubules and centromere-associated proteins. We used AlphaFold 2 (AF2) to obtain predictions of the Ndc80 'loop' structure and of the Ndc80 : Nuf2 globular head domains that interact with the Dam1 subunit of the heterodecameric DASH/Dam1 complex (Dam1c). The predictions guided design of crystallizable constructs, with structures close to the predicted ones. The Ndc80 'loop' is a stiff, alpha-helical 'switchback' structure; AF2 predictions and positions of preferential cleavage sites indicate that flexibility within the long Ndc80c rod occurs instead at a hinge closer to the globular head. Conserved stretches of the Dam1 C terminus bind Ndc80c such that phosphorylation of Dam1 serine residues 257, 265 and 292 by the mitotic kinase Ipl1/Aurora B can release this contact during error correction of mis-attached kinetochores. We integrate the structural results presented here into our current molecular model of the kinetochore-microtubule interface. The model illustrates how multiple interactions between Ndc80c, DASH/Dam1c and the microtubule lattice stabilize kinetochore attachments.
Structure of the Ndc80 complex and its interactions at the yeast kinetochore-microtubule interface.,Zahm JA, Jenni S, Harrison SC Open Biol. 2023 Mar;13(3):220378. doi: 10.1098/rsob.220378. Epub 2023 Mar 8. PMID:36883282[10]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
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- ↑ Joseph J, Liu ST, Jablonski SA, Yen TJ, Dasso M. The RanGAP1-RanBP2 complex is essential for microtubule-kinetochore interactions in vivo. Curr Biol. 2004 Apr 6;14(7):611-7. PMID:15062103 doi:http://dx.doi.org/10.1016/j.cub.2004.03.031
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- ↑ Bharadwaj R, Qi W, Yu H. Identification of two novel components of the human NDC80 kinetochore complex. J Biol Chem. 2004 Mar 26;279(13):13076-85. Epub 2003 Dec 29. PMID:14699129 doi:http://dx.doi.org/10.1074/jbc.M310224200
- ↑ DeLuca JG, Dong Y, Hergert P, Strauss J, Hickey JM, Salmon ED, McEwen BF. Hec1 and nuf2 are core components of the kinetochore outer plate essential for organizing microtubule attachment sites. Mol Biol Cell. 2005 Feb;16(2):519-31. Epub 2004 Nov 17. PMID:15548592 doi:http://dx.doi.org/10.1091/mbc.E04-09-0852
- ↑ Lin YT, Chen Y, Wu G, Lee WH. Hec1 sequentially recruits Zwint-1 and ZW10 to kinetochores for faithful chromosome segregation and spindle checkpoint control. Oncogene. 2006 Nov 2;25(52):6901-14. Epub 2006 May 29. PMID:16732327 doi:http://dx.doi.org/1209687
- ↑ Zahm JA, Jenni S, Harrison SC. Structure of the Ndc80 complex and its interactions at the yeast kinetochore-microtubule interface. Open Biol. 2023 Mar;13(3):220378. PMID:36883282 doi:10.1098/rsob.220378
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