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  Reconstitution of a 26-subunit human kinetochore reveals cooperative microtubule binding by CENP-OPQUR and NDC80.

Pesenti, M. E., Prumbaum, D., Auckland, P., Smith, C. M., Faesen, A. C., 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.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0002-5569-9 Version Permalink: http://hdl.handle.net/21.11116/0000-0003-AF71-9
Genre: Journal Article

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 Creators:
Pesenti, M. E., Author
Prumbaum, D., Author
Auckland, P., Author
Smith, C. M., Author
Faesen, A. C.1, Author              
Petrovic, A., Author
Erent, M., Author
Maffini, S., Author
Pentakota, S., Author
Weir, J. R., Author
Lin, Y. C., Author
Raunser, S., Author
McAinsh, A. D., Author
Musacchio, A., Author
Affiliations:
1Research Group Biochemistry of Signal Dynamics, MPI for Biophysical Chemistry, Max Planck Society, ou_2466695              

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Free keywords: CCAN; CENP-O; CENP-P; CENP-R; CENP-U; KMN network; centromere; constitutive centromere associated network; kinetochore; microtubule
 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.

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Language(s): eng - English
 Dates: 2018-08-302018-09-20
 Publication Status: Published in print
 Pages: -
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 Table of Contents: -
 Rev. Method: Peer
 Identifiers: DOI: 10.1016/j.molcel.2018.07.038
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Title: Molecular Cell
Source Genre: Journal
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Pages: - Volume / Issue: 71 (6) Sequence Number: - Start / End Page: 923 - 939 Identifier: -