Implications for kinetochore-microtubule attachment from the structure of an engineered Ndc80 complex.

@article{citeulike:2873097, abstract = {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.}, address = {Department of Experimental Oncology, European Institute of Oncology, Via Adamello 16, I 20139 Milan, Italy.}, author = {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, C. A. and Salmon, E. D. and Musacchio, A. }, citeulike-article-id = {2873097}, doi = {10.1016/j.cell.2008.03.020}, issn = {1097-4172}, journal = {Cell}, keywords = {complex, structure}, month = {May}, number = {3}, pages = {427--439}, posted-at = {2008-07-10 09:23:58}, priority = {2}, title = {Implications for kinetochore-microtubule attachment from the structure of an engineered Ndc80 complex.}, url = {http://dx.doi.org/10.1016/j.cell.2008.03.020}, volume = {133}, year = {2008} }

TY - JOUR ID - citeulike:2873097 L3 - citeulike-article-id:2873097 TI - Implications for kinetochore-microtubule attachment from the structure of an engineered Ndc80 complex. JF - Cell VL - 133 IS - 3 SP - 427 EP - 439 AD - Department of Experimental Oncology, European Institute of Oncology, Via Adamello 16, I 20139 Milan, Italy. SN - 1097-4172 N2 - 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. KW - complex KW - structure AU - Ciferri, C AU - Pasqualato, S AU - Screpanti, E AU - Varetti, G AU - Santaguida, S AU - Dos Reis, G AU - Maiolica, A AU - Polka, J AU - De Luca, JG AU - De Wulf, P AU - Salek, M AU - Rappsilber, J AU - Moores, CA AU - Salmon, ED AU - Musacchio, A PY - 2008/05/02/ UR - http://dx.doi.org/10.1016/j.cell.2008.03.020 ER -