Implications for Kinetochore-Microtubule attachment from the structure of an engineered Ndc80 complex
Ciferri, C. and Pasqualato, S. and Screpanti, E. and Varetti, G. and Santaguida, S. and dos Reis, G. and Maiolica, A. and Polka, J. and de Luca, J.G. and de Wulf, P. and Salek, M. and Rappsilber, J. and Moores, Carolyn A. and Salmon, E.D. and Musacchio, A. (2008) Implications for Kinetochore-Microtubule attachment from the structure of an engineered Ndc80 complex. Cell 133 (3), pp. 427-439. ISSN 0092-8674.
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.
|School:||Birkbeck Schools and Departments > School of Science > Biological Sciences|
|Research Centre:||Structural Molecular Biology, Institute of (ISMB)|
|Date Deposited:||04 Aug 2010 14:09|
|Last Modified:||06 Dec 2016 11:12|
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