Structural highlights
Function
[SKA1_HUMAN] Component of the SKA1 complex, a microtubule-binding subcomplex of the outer kinetochore that is essential for proper chromosome segregation. Required for timely anaphase onset during mitosis, when chromosomes undergo bipolar attachment on spindle microtubules leading to silencing of the spindle checkpoint. The SKA1 complex is a direct component of the kinetochore-microtubule interface and directly associates with microtubules as oligomeric assemblies. The complex facilitates the processive movement of microspheres along a microtubule in a depolymerization-coupled manner. In the complex, it mediates the interaction with microtubules.[1] [2]
Publication Abstract from PubMed
The ability of kinetochores (KTs) to maintain stable attachments to dynamic microtubule structures ('straight' during microtubule polymerization and 'curved' during microtubule depolymerization) is an essential requirement for accurate chromosome segregation. Here we show that the kinetochore-associated Ska complex interacts with tubulin monomers via the carboxy-terminal winged-helix domain of Ska1, providing the structural basis for the ability to bind both straight and curved microtubule structures. This contrasts with the Ndc80 complex, which binds straight microtubules by recognizing the dimeric interface of tubulin. The Ska1 microtubule-binding domain interacts with tubulins using multiple contact sites that allow the Ska complex to bind microtubules in multiple modes. Disrupting either the flexibility or the tubulin contact sites of the Ska1 microtubule-binding domain perturbs normal mitotic progression, explaining the critical role of the Ska complex in maintaining a firm grip on dynamic microtubules.
Structural basis for microtubule recognition by the human kinetochore Ska complex.,Abad MA, Medina B, Santamaria A, Zou J, Plasberg-Hill C, Madhumalar A, Jayachandran U, Redli PM, Rappsilber J, Nigg EA, Jeyaprakash AA Nat Commun. 2014 Jan 13;5:2964. doi: 10.1038/ncomms3964. PMID:24413531[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Hanisch A, Sillje HH, Nigg EA. Timely anaphase onset requires a novel spindle and kinetochore complex comprising Ska1 and Ska2. EMBO J. 2006 Nov 29;25(23):5504-15. Epub 2006 Nov 9. PMID:17093495 doi:http://dx.doi.org/10.1038/sj.emboj.7601426
- ↑ Welburn JP, Grishchuk EL, Backer CB, Wilson-Kubalek EM, Yates JR 3rd, Cheeseman IM. The human kinetochore Ska1 complex facilitates microtubule depolymerization-coupled motility. Dev Cell. 2009 Mar;16(3):374-85. PMID:19289083 doi:http://dx.doi.org/S1534-5807(09)00039-2
- ↑ Abad MA, Medina B, Santamaria A, Zou J, Plasberg-Hill C, Madhumalar A, Jayachandran U, Redli PM, Rappsilber J, Nigg EA, Jeyaprakash AA. Structural basis for microtubule recognition by the human kinetochore Ska complex. Nat Commun. 2014 Jan 13;5:2964. doi: 10.1038/ncomms3964. PMID:24413531 doi:http://dx.doi.org/10.1038/ncomms3964
