5Z23

Crystal structure of the nucleosome containing a chimeric histone H3/CENP-A CATD

Summary for 5Z23

• Entry DOI: 10.2210/pdb5z23/pdb
• Descriptor: Histone H3.1,Histone H3-like centromeric protein A,Histone H3.1, Histone H4, Histone H2A type 1-B/E, ... (5 entities in total)
• Functional Keywords: nucleosome, chromosome, cenp-a, centromere, dna binding protein, dna binding protein-dna complex, dna binding protein/dna
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 10
• Total formula weight: 211118.83

Authors

Arimura, Y.,Tachiwana, H.,Takagi, H. (deposition date: 2017-12-28, release date: 2019-02-13, Last modification date: 2024-10-16)

Primary citation

Arimura, Y.,Tachiwana, H.,Takagi, H.,Hori, T.,Kimura, H.,Fukagawa, T.,Kurumizaka, H.
The CENP-A centromere targeting domain facilitates H4K20 monomethylation in the nucleosome by structural polymorphism.
Nat Commun, 10:576-576, 2019

PubMed Abstract: Centromeric nucleosomes are composed of the centromere-specific histone H3 variant CENP-A and the core histones H2A, H2B, and H4. To establish a functional kinetochore, histone H4 lysine-20 (H4K20) must be monomethylated, but the underlying mechanism has remained enigmatic. To provide structural insights into H4K20 methylation, we here solve the crystal structure of a nucleosome containing an H3.1-CENP-A chimera, H3.1, which has a CENP-A centromere targeting domain and preserves essential CENP-A functions in vivo. Compared to the canonical H3.1 nucleosome, the H3.1 nucleosome exhibits conformational changes in the H4 N-terminal tail leading to a relocation of H4K20. In particular, the H4 N-terminal tail interacts with glutamine-76 and aspartate-77 of canonical H3.1 while these interactions are cancelled in the presence of the CENP-A-specific residues valine-76 and lysine-77. Mutations of valine-76 and lysine-77 impair H4K20 monomethylation both in vitro and in vivo. These findings suggest that a CENP-A-mediated structural polymorphism may explain the preferential H4K20 monomethylation in centromeric nucleosomes.

PubMed: 30718488
DOI: 10.1038/s41467-019-08314-x

Experimental method

X-RAY DIFFRACTION (2.73 Å)