Structural analysis of Rtt106p reveals a DNA binding role required for heterochromatin silencing

Yiwei Liu; Hongda Huang; Bo O Zhou; Shan-Shan Wang; Yingxia Hu; Xu Li; Jianping Liu; Jianye Zang; Liwen Niu; Jihui Wu; Jin-Qiu Zhou; Maikun Teng; Yunyu Shi

doi:10.1074/jbc.M109.055996

Structural analysis of Rtt106p reveals a DNA binding role required for heterochromatin silencing

J Biol Chem. 2010 Feb 5;285(6):4251-4262. doi: 10.1074/jbc.M109.055996. Epub 2009 Dec 10.

Authors

Yiwei Liu¹, Hongda Huang¹, Bo O Zhou², Shan-Shan Wang², Yingxia Hu¹, Xu Li¹, Jianping Liu¹, Jianye Zang¹, Liwen Niu¹, Jihui Wu¹, Jin-Qiu Zhou², Maikun Teng³, Yunyu Shi⁴

Affiliations

¹ 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.
² 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.
³ 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: [email protected].
⁴ 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: [email protected].

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Sequence
Binding Sites
Blotting, Western
Crystallography, X-Ray
DNA, Fungal / genetics
DNA, Fungal / metabolism
DNA-Binding Proteins / chemistry
DNA-Binding Proteins / genetics
DNA-Binding Proteins / metabolism*
Gene Expression Regulation, Fungal*
Heterochromatin / genetics*
Histones / metabolism
Models, Biological
Models, Molecular
Molecular Chaperones / chemistry
Molecular Chaperones / genetics
Molecular Chaperones / metabolism*
Molecular Sequence Data
Mutation
Nucleosomes / metabolism
Protein Binding
Protein Structure, Tertiary
Saccharomyces cerevisiae / genetics
Saccharomyces cerevisiae / metabolism
Saccharomyces cerevisiae Proteins / chemistry
Saccharomyces cerevisiae Proteins / genetics
Saccharomyces cerevisiae Proteins / metabolism*
Sequence Homology, Amino Acid
Silent Information Regulator Proteins, Saccharomyces cerevisiae / genetics
Silent Information Regulator Proteins, Saccharomyces cerevisiae / metabolism

Substances

DNA, Fungal
DNA-Binding Proteins
Heterochromatin
Histones
Molecular Chaperones
Nucleosomes
Rtt106 protein, S cerevisiae
Saccharomyces cerevisiae Proteins
Silent Information Regulator Proteins, Saccharomyces cerevisiae

Associated data

PDB/3GYO
PDB/3GYP