Structural mechanisms of centromeric nucleosome recognition by the kinetochore protein CENP-N
- 19 January 2018
- journal article
- research article
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 359 (6373), 339-343
- https://doi.org/10.1126/science.aar2781
Abstract
Accurate chromosome segregation requires the proper assembly of kinetochore proteins. A key step in this process is the recognition of the histone H3 variant CENP-A in the centromeric nucleosome by the kinetochore protein CENP-N. We report cryo–electron microscopy (cryo-EM), biophysical, biochemical, and cell biological studies of the interaction between the CENP-A nucleosome and CENP-N. We show that human CENP-N confers binding specificity through interactions with the L1 loop of CENP-A, stabilized by electrostatic interactions with the nucleosomal DNA. Mutational analyses demonstrate analogous interactions in Xenopus, which are further supported by residue-swapping experiments involving the L1 loop of CENP-A. Our results are consistent with the coevolution of CENP-N and CENP-A and establish the structural basis for recognition of the CENP-A nucleosome to enable kinetochore assembly and centromeric chromatin organization.This publication has 55 references indexed in Scilit:
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