Structural analysis of Rtt106p reveals a DNA binding role required for heterochromatin silencing.
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.
Liu
Yiwei
Y
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.
Huang
Hongda
H
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.
Zhou
Bo O
BO
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.
Wang
Shan-Shan
SS
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.
Hu
Yingxia
Y
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.
Li
Xu
X
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.
Liu
Jianping
J
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.
Zang
Jianye
J
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.
Niu
Liwen
L
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.
Wu
Jihui
J
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.
Zhou
Jin-Qiu
JQ
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.
Teng
Maikun
M
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. Electronic address: mkteng@ustc.edu.cn.
Shi
Yunyu
Y
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. Electronic address: yyshi@ustc.edu.cn.
D000595:Amino Acid Sequence; D001665:Binding Sites; D015153:Blotting, Western; D018360:Crystallography, X-Ray; D004271:DNA, Fungal / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D006570:Heterochromatin / Q000235:genetics*; D006657:Histones / Q000378:metabolism; D008954:Models, Biological; D008958:Models, Molecular; D018832:Molecular Chaperones / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009154:Mutation; D009707:Nucleosomes / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism
D004271:DNA, Fungal; D004268:DNA-Binding Proteins; D006570:Heterochromatin; D006657:Histones; D018832:Molecular Chaperones; D009707:Nucleosomes; C505157:Rtt106 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae