title: Crystal structure and stable property of the cancer-associated heterotypic nucleosome containing CENP-A and H3.3.
abstract: 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.
authors.affiliation: Laboratory of Structural Biology, Graduate School of Advanced Science and Engineering, Waseda University, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Arimura
authors.affiliation: Laboratory of Structural Biology, Graduate School of Advanced Science and Engineering, Waseda University, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480, Japan.
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Shirayama
authors.affiliation: Laboratory of Structural Biology, Graduate School of Advanced Science and Engineering, Waseda University, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Horikoshi
authors.affiliation: Laboratory of Structural Biology, Graduate School of Advanced Science and Engineering, Waseda University, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480, Japan.
authors.forename: Risa
authors.initials: R
authors.lastname: Fujita
authors.affiliation: Laboratory of Structural Biology, Graduate School of Advanced Science and Engineering, Waseda University, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Taguchi
authors.affiliation: 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.
authors.forename: Wataru
authors.initials: W
authors.lastname: Kagawa
authors.affiliation: Department of Molecular Genetics, National Institute of Genetics, Mishima, Shizuoka 411-8540, Japan.
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Fukagawa
authors.affiliation: 1] Institut Curie, Centre de Recherche, Paris, F-75248 France [2] CNRS, UMR3664, Paris, F-75248 France.
authors.forename: Geneviève
authors.initials: G
authors.lastname: Almouzni
authors.affiliation: Laboratory of Structural Biology, Graduate School of Advanced Science and Engineering, Waseda University, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Kurumizaka
mesh_terms: D020816:Amino Acid Motifs; D001324:Autoantigens / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites; D000076247:Centromere Protein A; D002868:Chromosomal Proteins, Non-Histone / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D006657:Histones / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009707:Nucleosomes / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D055503:Protein Multimerization; D055550:Protein Stability; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D001324:Autoantigens; C000619700:CENPA protein, human; D000076247:Centromere Protein A; D002868:Chromosomal Proteins, Non-Histone; D006657:Histones; D009707:Nucleosomes; D011994:Recombinant Proteins; C060905:centromere protein C