CENP-T-W-S-X forms a unique centromeric chromatin structure with a histone-like fold.

CENP-T-W-S-X forms a unique centromeric chromatin structure with a histone-like fold.
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DOI:
10.1016/j.cell.2011.11.061
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发表时间:
2012-02-03
期刊:
影响因子:
64.5
通讯作者:
Fukagawa T
Fukagawa T
中科院分区:
生物学1区
文献类型:
--
作者:
Nishino T;Takeuchi K;Gascoigne KE;Suzuki A;Hori T;Oyama T;Morikawa K;Cheeseman IM;Fukagawa T

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多蛋白质动粒复合物必须在每条染色体上的特定位点组装以实现精确的染色体分离。确定DNA-蛋白质相互作用的性质,指定动粒的位置,并为动粒形成提供支架仍然是关键目标。在这里,我们证明了含有CENP-T-W和CENP-S-X复合物的着丝粒组蛋白折叠共组装形成稳定的CENP-T-W-S-X异四聚体。对单个复合物和异四聚体的高分辨率结构分析揭示了与其他含有组蛋白折叠的复合物(包括核小体内的典型组蛋白)的相似性。CENP-T-W-S-X异源四聚体结合并超螺旋DNA。设计为损害异源四聚体或异源四聚体周围的DNA-蛋白质接触的突变体强烈降低体外DNA结合和超螺旋活性,并损害体内动粒组装。这些数据表明,CENP-T-W-S-X复合物形成了独特的核小体样结构,以产生与DNA的接触,将“组蛋白密码”扩展到经典核小体蛋白之外。
The multi-protein kinetochore complex must assemble at a specific site on each chromosome to achieve accurate chromosome segregation. Defining the nature of the DNA-protein interactions that specify the position of the kinetochore and provide a scaffold for kinetochore formation remain key goals. Here, we demonstrate that the centromeric histone-fold containing CENP-T-W and CENP-S-X complexes co-assemble to form a stable CENP-T-W-S-X heterotetramer. High-resolution structural analysis of the individual complexes and the heterotetramer reveals similarity to other histone fold-containing complexes including canonical histones within a nucleosome. The CENP-T-W-S-X heterotetramer binds to and supercoils DNA. Mutants designed to compromise heterotetramerization or the DNA-protein contacts around the heterotetramer strongly reduce the DNA binding and supercoiling activities in vitro and compromise kinetochore assembly in vivo. These data suggest that the CENP-T-W-S-X complex forms a unique nucleosome-like structure to generate contacts with DNA, extending the “histone code” beyond canonical nucleosome proteins.
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