Structural basis of silencing: Sir3 BAH domain in complex with a nucleosome at 3.0 Å resolution.

Publication Type:

Journal Article


Science, Volume 334, Issue 6058, p.977-82 (2011)


Acetylation, Amino Acid Sequence, Binding Sites, Chemical Phenomena, Crystallography, X-Ray, Gene Silencing, Histones, Hydrogen Bonding, Methylation, Models, Molecular, Molecular Sequence Data, Mutagenesis, Mutant Proteins, Nucleosomes, Protein Folding, Protein Interaction Domains and Motifs, Protein Multimerization, Protein Structure, Tertiary, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Silent Information Regulator Proteins, Saccharomyces cerevisiae, Static Electricity


<p>Gene silencing is essential for regulating cell fate in eukaryotes. Altered chromatin architectures contribute to maintaining the silenced state in a variety of species. The silent information regulator (Sir) proteins regulate mating type in Saccharomyces cerevisiae. One of these proteins, Sir3, interacts directly with the nucleosome to help generate silenced domains. We determined the crystal structure of a complex of the yeast Sir3 BAH (bromo-associated homology) domain and the nucleosome core particle at 3.0 angstrom resolution. We see multiple molecular interactions between the protein surfaces of the nucleosome and the BAH domain that explain numerous genetic mutations. These interactions are accompanied by structural rearrangements in both the nucleosome and the BAH domain. The structure explains how covalent modifications on H4K16 and H3K79 regulate formation of a silencing complex that contains the nucleosome as a central component.</p>