5z23
From Proteopedia
Crystal structure of the nucleosome containing a chimeric histone H3/CENP-A CATD
Structural highlights
FunctionH31_HUMAN CENPA_HUMAN Histone H3-like variant which exclusively replaces conventional H3 in the nucleosome core of centromeric chromatin at the inner plate of the kinetochore. Required for recruitment and assembly of kinetochore proteins, mitotic progression and chromosome segregation. May serve as an epigenetic mark that propagates centromere identity through replication and cell division. The CENPA-H4 heterotetramer can bind DNA by itself (in vitro).[1] [2] Publication Abstract from PubMedCentromeric 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(CATD), 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(CATD) 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. The CENP-A centromere targeting domain facilitates H4K20 monomethylation in the nucleosome by structural polymorphism.,Arimura Y, Tachiwana H, Takagi H, Hori T, Kimura H, Fukagawa T, Kurumizaka H Nat Commun. 2019 Feb 4;10(1):576. doi: 10.1038/s41467-019-08314-x. PMID:30718488[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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