| 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] [NUF2_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.[10] [11] [12] [13] [14] [15] [16]
Evolutionary Conservation
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Publication Abstract from PubMed
Kinetochores are proteinaceous assemblies that mediate the interaction of chromosomes with the mitotic spindle. The 180 kDa Ndc80 complex is a direct point of contact between kinetochores and microtubules. Its four subunits contain coiled coils and form an elongated rod structure with functional globular domains at either end. We crystallized an engineered "bonsai" Ndc80 complex containing a shortened rod domain but retaining the globular domains required for kinetochore localization and microtubule binding. The structure reveals a microtubule-binding interface containing a pair of tightly interacting calponin-homology (CH) domains with a previously unknown arrangement. The interaction with microtubules is cooperative and predominantly electrostatic. It involves positive charges in the CH domains and in the N-terminal tail of the Ndc80 subunit and negative charges in tubulin C-terminal tails and is regulated by the Aurora B kinase. We discuss our results with reference to current models of kinetochore-microtubule attachment and centromere organization.
Implications for kinetochore-microtubule attachment from the structure of an engineered Ndc80 complex.,Ciferri C, Pasqualato S, Screpanti E, Varetti G, Santaguida S, Dos Reis G, Maiolica A, Polka J, De Luca JG, De Wulf P, Salek M, Rappsilber J, Moores CA, Salmon ED, Musacchio A Cell. 2008 May 2;133(3):427-39. PMID:18455984[17]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
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- ↑ Martin-Lluesma S, Stucke VM, Nigg EA. Role of Hec1 in spindle checkpoint signaling and kinetochore recruitment of Mad1/Mad2. Science. 2002 Sep 27;297(5590):2267-70. PMID:12351790 doi:http://dx.doi.org/10.1126/science.1075596
- ↑ DeLuca JG, Howell BJ, Canman JC, Hickey JM, Fang G, Salmon ED. Nuf2 and Hec1 are required for retention of the checkpoint proteins Mad1 and Mad2 to kinetochores. Curr Biol. 2003 Dec 2;13(23):2103-9. PMID:14654001
- ↑ Stucke VM, Baumann C, Nigg EA. Kinetochore localization and microtubule interaction of the human spindle checkpoint kinase Mps1. Chromosoma. 2004 Aug;113(1):1-15. Epub 2004 Jul 3. PMID:15235793 doi:http://dx.doi.org/10.1007/s00412-004-0288-2
- ↑ 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
- ↑ Meraldi P, Draviam VM, Sorger PK. Timing and checkpoints in the regulation of mitotic progression. Dev Cell. 2004 Jul;7(1):45-60. PMID:15239953 doi:http://dx.doi.org/10.1016/j.devcel.2004.06.006
- ↑ 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
- ↑ DeLuca JG, Moree B, Hickey JM, Kilmartin JV, Salmon ED. hNuf2 inhibition blocks stable kinetochore-microtubule attachment and induces mitotic cell death in HeLa cells. J Cell Biol. 2002 Nov 25;159(4):549-55. Epub 2002 Nov 18. PMID:12438418 doi:http://dx.doi.org/10.1083/jcb.200208159
- ↑ DeLuca JG, Howell BJ, Canman JC, Hickey JM, Fang G, Salmon ED. Nuf2 and Hec1 are required for retention of the checkpoint proteins Mad1 and Mad2 to kinetochores. Curr Biol. 2003 Dec 2;13(23):2103-9. PMID:14654001
- ↑ Stucke VM, Baumann C, Nigg EA. Kinetochore localization and microtubule interaction of the human spindle checkpoint kinase Mps1. Chromosoma. 2004 Aug;113(1):1-15. Epub 2004 Jul 3. PMID:15235793 doi:http://dx.doi.org/10.1007/s00412-004-0288-2
- ↑ 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
- ↑ Meraldi P, Draviam VM, Sorger PK. Timing and checkpoints in the regulation of mitotic progression. Dev Cell. 2004 Jul;7(1):45-60. PMID:15239953 doi:http://dx.doi.org/10.1016/j.devcel.2004.06.006
- ↑ 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
- ↑ Liu D, Ding X, Du J, Cai X, Huang Y, Ward T, Shaw A, Yang Y, Hu R, Jin C, Yao X. Human NUF2 interacts with centromere-associated protein E and is essential for a stable spindle microtubule-kinetochore attachment. J Biol Chem. 2007 Jul 20;282(29):21415-24. Epub 2007 May 29. PMID:17535814 doi:http://dx.doi.org/10.1074/jbc.M609026200
- ↑ Ciferri C, Pasqualato S, Screpanti E, Varetti G, Santaguida S, Dos Reis G, Maiolica A, Polka J, De Luca JG, De Wulf P, Salek M, Rappsilber J, Moores CA, Salmon ED, Musacchio A. Implications for kinetochore-microtubule attachment from the structure of an engineered Ndc80 complex. Cell. 2008 May 2;133(3):427-39. PMID:18455984 doi:http://dx.doi.org/S0092-8674(08)00401-7
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