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bioRxiv · 10.1101/2022.01.06.475204

Structure of the human inner kinetochore CCAN complex and its significance for human centromere organization

Pesenti, M. E.·Raisch, T.·Conti, D.·Hoffmann, I.·Vogt, D.·Prumbaum, D.·Vetter, I. R.·Raunser, S.·Musacchio, A.
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Abstract

Centromeres are specialized chromosome loci that seed the kinetochore, a large protein complex that effects chromosome segregation. The organization of the interface between the kinetochore and the specialized centromeric chromatin, marked by the histone H3 variant CENP-A, remains incompletely understood. A 16-subunit complex, the constitutive centromere associated network (CCAN), bridges CENP-A to the spindle-binding moiety of the kinetochore. Here, we report a cryo-electron microscopy structure of human CCAN. We highlight unique features such as the pseudo GTPase CENP-M and report how a crucial CENP-C motif binds the CENP-LN complex. The CCAN structure has also important implications for the mechanism of specific recognition of the CENP-A nucleosome. A supported model depicts the interaction as fuzzy and identifies the disordered CCAN subunit CENP-C as only determinant of specificity. A more speculative model identifies both CENP-C and CENP-N as specificity determinants, but implies CENP-A may be in a hemisome rather than in a classical octamer.

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Pesenti, M. E., Raisch, T., Conti, D., Hoffmann, I., Vogt, D., Prumbaum, D., Vetter, I. R., Raunser, S., Musacchio, A.. 2022-01-06. Structure of the human inner kinetochore CCAN complex and its significance for human centromere organization. https://doi.org/10.1101/2022.01.06.475204

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