| Literature DB >> 33463726 |
Mariko Ariyoshi1, Fumiaki Makino1,2, Reito Watanabe1, Reiko Nakagawa3, Takayuki Kato1,4, Keiichi Namba1,5, Yasuhiro Arimura6, Risa Fujita6, Hitoshi Kurumizaka6, Ei-Ichi Okumura7, Masatoshi Hara1, Tatsuo Fukagawa1.
Abstract
The CENP-A nucleosome is a key structure for kinetochore assembly. Once the CENP-A nucleosome is established in the centromere, additional proteins recognize the CENP-A nucleosome to form a kinetochore. CENP-C and CENP-N are CENP-A binding proteins. We previously demonstrated that vertebrate CENP-C binding to the CENP-A nucleosome is regulated by CDK1-mediated CENP-C phosphorylation. However, it is still unknown how the phosphorylation of CENP-C regulates its binding to CENP-A. It is also not completely understood how and whether CENP-C and CENP-N act together on the CENP-A nucleosome. Here, using cryo-electron microscopy (cryo-EM) in combination with biochemical approaches, we reveal a stable CENP-A nucleosome-binding mode of CENP-C through unique regions. The chicken CENP-C structure bound to the CENP-A nucleosome is stabilized by an intramolecular link through the phosphorylated CENP-C residue. The stable CENP-A-CENP-C complex excludes CENP-N from the CENP-A nucleosome. These findings provide mechanistic insights into the dynamic kinetochore assembly regulated by CDK1-mediated CENP-C phosphorylation.Entities:
Keywords: CENP-A; CENP-C; Cryo-EM; kinetochore; phosphorylation
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Year: 2021 PMID： 33463726 PMCID： PMC7917552 DOI： 10.15252/embj.2020105671
Source DB: PubMed Journal: EMBO J ISSN： 0261-4189 Impact factor: 11.598