3AN2

The structure of the centromeric nucleosome containing CENP-A

3AN2 の概要

• エントリーDOI: 10.2210/pdb3an2/pdb
• 分子名称: Histone H3-like centromeric protein A, Histone H4, Histone H2A type 1-B/E, ... (5 entities in total)
• 機能のキーワード: histone fold, dna binding, nucleus, structural protein-dna complex, structural protein/dna
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Nucleus: P49450 P04908 P06899
• タンパク質・核酸の鎖数: 10
• 化学式量合計: 204311.40

構造登録者

Tachiwana, H.,Kagawa, W.,Shiga, T.,Saito, K.,Osakabe, A.,Hayashi-Takanaka, Y.,Park, S.-Y.,Kimura, H.,Kurumizaka, H. (登録日: 2010-08-27, 公開日: 2011-07-20, 最終更新日: 2024-11-13)

主引用文献

Tachiwana, H.,Kagawa, W.,Shiga, T.,Osakabe, A.,Miya, Y.,Saito, K.,Hayashi-Takanaka, Y.,Oda, T.,Sato, M.,Park, S.-Y.,Kimura, H.,Kurumizaka, H.
Crystal structure of the human centromeric nucleosome containing CENP-A
Nature, 476:232-235, 2011

PubMed Abstract: In eukaryotes, accurate chromosome segregation during mitosis and meiosis is coordinated by kinetochores, which are unique chromosomal sites for microtubule attachment. Centromeres specify the kinetochore formation sites on individual chromosomes, and are epigenetically marked by the assembly of nucleosomes containing the centromere-specific histone H3 variant, CENP-A. Although the underlying mechanism is unclear, centromere inheritance is probably dictated by the architecture of the centromeric nucleosome. Here we report the crystal structure of the human centromeric nucleosome containing CENP-A and its cognate α-satellite DNA derivative (147 base pairs). In the human CENP-A nucleosome, the DNA is wrapped around the histone octamer, consisting of two each of histones H2A, H2B, H4 and CENP-A, in a left-handed orientation. However, unlike the canonical H3 nucleosome, only the central 121 base pairs of the DNA are visible. The thirteen base pairs from both ends of the DNA are invisible in the crystal structure, and the αN helix of CENP-A is shorter than that of H3, which is known to be important for the orientation of the DNA ends in the canonical H3 nucleosome. A structural comparison of the CENP-A and H3 nucleosomes revealed that CENP-A contains two extra amino acid residues (Arg 80 and Gly 81) in the loop 1 region, which is completely exposed to the solvent. Mutations of the CENP-A loop 1 residues reduced CENP-A retention at the centromeres in human cells. Therefore, the CENP-A loop 1 may function in stabilizing the centromeric chromatin containing CENP-A, possibly by providing a binding site for trans-acting factors. The structure provides the first atomic-resolution picture of the centromere-specific nucleosome.

PubMed: 21743476
DOI: 10.1038/nature10258

実験手法

X-RAY DIFFRACTION (3.6 Å)