Reconstitution of a 26-Subunit Human Kinetochore Reveals Cooperative 
Microtubule Binding by CENP-OPQUR and NDC80.

Pesenti, ME; Prumbaum, D; Auckla , P; Smith, CM; Faesen, AC; Petrovic, A; Erent, M; Maffini, S; Pentakota, S; Weir, JR; Lin, Y-C; Raunser, R; McAinsh, AD; Musacchio, A

doi:10.1016/j.molcel.2018.07.038

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Reconstitution of a 26-Subunit Human Kinetochore Reveals Cooperative Microtubule Binding by CENP-OPQUR and NDC80.

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Pesenti, M., Prumbaum, D., Auckla, P., Smith, C., Faesen, A., Petrovic, A., et al. (2018). Reconstitution of a 26-Subunit Human Kinetochore Reveals Cooperative Microtubule Binding by CENP-OPQUR and NDC80. Molecular Cell, 71(6), 923-939. doi:10.1016/j.molcel.2018.07.038.

Cite as: https://hdl.handle.net/21.11116/0000-0004-6642-F

Abstract

The approximately thirty core subunits of kinetochores assemble on centromeric chromatin containing the histone H3 variant CENP-A and connect chromosomes with spindle microtubules. The chromatin proximal 16-subunit CCAN (constitutive centromere associated network) creates a mechanically stable bridge between CENP-A and the kinetochore’s microtubule-binding machinery, the 10-subunit KMN assembly. Here, we reconstituted a stoichiometric 11-subunit human CCAN core that forms when the CENP-OPQUR complex binds to a joint interface on the CENP-HIKM and CENP-LN complexes. The resulting CCAN particle is globular and connects KMN and CENP-A in a 26-subunit recombinant particle. The disordered, basic N-terminal tail of CENP-Q binds microtubules and promotes accurate chromosome alignment, cooperating with KMN in microtubule binding. The N-terminal basic tail of the NDC80 complex, the microtubule-binding subunit of KMN, can functionally replace the CENP-Q tail. Our work dissects the connectivity and architecture of CCAN and reveals unexpected functional similarities between CENP-OPQUR and the NDC80 complex.