From the Hefei National Laboratory for Physical Sciences at Microscale and School of Life Science, University of Science and Technology of China, Hefei, Anhui 230026 and.
the State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, the Graduate School, Chinese Academy of Sciences, Shanghai 200031, China.
J Biol Chem. 2010 Feb 5;285(6):4251-4262. doi: 10.1074/jbc.M109.055996. Epub 2009 Dec 10.
Rtt106p is a Saccharomyces cerevisiae histone chaperone with roles in heterochromatin silencing and nucleosome assembly. The molecular mechanism by which Rtt106p engages in chromatin dynamics remains unclear. Here, we report the 2.5 A crystal structure of the core domain of Rtt106p, which adopts an unusual "double pleckstrin homology" domain architecture that represents a novel structural mode for histone chaperones. A histone H3-H4-binding region and a novel double-stranded DNA-binding region have been identified. Mutagenesis studies reveal that the histone and DNA binding activities of Rtt106p are involved in Sir protein-mediated heterochromatin formation. Our results uncover the structural basis of the diverse functions of Rtt106p and provide new insights into its cellular roles.
Rtt106p 是酿酒酵母中的一种组蛋白伴侣，在异染色质沉默和核小体组装中发挥作用。Rtt106p 参与染色质动力学的分子机制尚不清楚。在这里，我们报告了 Rtt106p 核心结构域的 2.5A 晶体结构，该结构采用了一种不寻常的“双 pleckstrin 同源”结构域架构，代表了组蛋白伴侣的一种新的结构模式。已经鉴定出一个组蛋白 H3-H4 结合区域和一个新的双链 DNA 结合区域。突变研究表明，Rtt106p 的组蛋白和 DNA 结合活性参与了 Sir 蛋白介导的异染色质形成。我们的结果揭示了 Rtt106p 多种功能的结构基础，并为其细胞功能提供了新的见解。
