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PMID: 22096199 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

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

Science (New York, N.Y.) ·Vol. 334 ·No. 6058 ·2011-11-18 ·Pages 977-82

Armache KJ, Garlick JD, Canzio D, Narlikar GJ, Kingston RE

Abstract

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.

MeSH Terms
Acetylation Amino Acid Sequence Binding Sites Chemical Phenomena Crystallography, X-Ray Gene Silencing Histones/chemistry,metabolism Hydrogen Bonding Methylation Models, Molecular Molecular Sequence Data Mutagenesis Mutant Proteins/chemistry,metabolism Nucleosomes/chemistry,metabolism,ultrastructure Protein Folding Protein Interaction Domains and Motifs Protein Multimerization Protein Structure, Tertiary Saccharomyces cerevisiae/chemistry,genetics,metabolism Saccharomyces cerevisiae Proteins/chemistry,metabolism Silent Information Regulator Proteins, Saccharomyces cerevisiae/chemistry,genetics,metabolism Static Electricity
Chemicals
Histones Mutant Proteins Nucleosomes SIR3 protein, S cerevisiae Saccharomyces cerevisiae Proteins Silent Information Regulator Proteins, Saccharomyces cerevisiae
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Armache Karim-Jean
Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA.
Garlick Joseph D
Canzio Daniele
Narlikar Geeta J
Kingston Robert E
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Article Info
Journal
Science (New York, N.Y.)
Abbr.
Science
ISSN
1095-9203
DOI
10.1126/science.1210915
Published
2011-11-18
Pages
977-82
Language
English
Region
United States
NLM ID
0404511
PMCID
PMC4098850
Subset
IM
Grants
NCRR NIH HHS · P41 RR012408 · United States
NIGMS NIH HHS · R01 GM043901 · United States
NIGMS NIH HHS · R37 GM048405 · United States
NIGMS NIH HHS · GM043901 · United States
Databases
PDB
3TU4
External Links
PubMed source DOI: 10.1126/science.1210915 PMC Full Text View journal details
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