Cryo-EM structure of the CENP-A nucleosome in complex with phosphorylated CENP-C.
EMBO J
; 40(5): e105671, 2021 03 01.
Article
in En
| MEDLINE
| ID: mdl-33463726
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Chromosomal Proteins, Non-Histone
/
Nucleosomes
/
Centromere
/
Kinetochores
/
Cryoelectron Microscopy
/
Centromere Protein A
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
EMBO J
Year:
2021
Document type:
Article
Affiliation country: