Arimura Yasuhiro, Shirayama Kazuyoshi, Horikoshi Naoki, Fujita Risa, Taguchi Hiroyuki, Kagawa Wataru, Fukagawa Tatsuo, Almouzni Geneviève, Kurumizaka Hitoshi
Laboratory of Structural Biology, Graduate School of Advanced Science and Engineering, Waseda University, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480, Japan.
1] Laboratory of Structural Biology, Graduate School of Advanced Science and Engineering, Waseda University, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480, Japan [2] Program in Chemistry and Life Science, School of Science and Engineering, Meisei University, 2-1-1 Hodokubo, Hino-shi, Tokyo 191-8506, Japan.
Sci Rep. 2014 Nov 19;4:7115. doi: 10.1038/srep07115.
The centromere-specific histone H3 variant, CENP-A, is overexpressed in particular aggressive cancer cells, where it can be mislocalized ectopically in the form of heterotypic nucleosomes containing H3.3. In the present study, we report the crystal structure of the heterotypic CENP-A/H3.3 particle and reveal its "hybrid structure", in which the physical characteristics of CENP-A and H3.3 are conserved independently within the same particle. The CENP-A/H3.3 nucleosome forms an unexpectedly stable structure as compared to the CENP-A nucleosome, and allows the binding of the essential centromeric protein, CENP-C, which is ectopically mislocalized in the chromosomes of CENP-A overexpressing cells.
着丝粒特异性组蛋白H3变体CENP-A在某些侵袭性癌细胞中过度表达，在这些细胞中，它可能以含有H3.3的异型核小体形式异位定位错误。在本研究中，我们报告了异型CENP-A/H3.3颗粒的晶体结构，并揭示了其“混合结构”，其中CENP-A和H3.3的物理特征在同一颗粒内独立保守。与CENP-A核小体相比，CENP-A/H3.3核小体形成了意想不到的稳定结构，并允许必需的着丝粒蛋白CENP-C结合，而CENP-C在CENP-A过表达细胞的染色体中异位定位错误。
