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Structural basis for origin recognition complex 1 protein-silence information regulator 1 protein interaction in epigenetic silencing.

http://www.ncbi.nlm.nih.gov/pubmed/15937111

The interaction between silence information regulator 1 protein (Sir1p) and origin recognition complex 1 protein (Orc1p), the largest subunit of the origin recognition complex, plays an important role in the establishment of transcriptional silencing at the cryptic mating-type gene loci in Saccharomyces cerevisiae. Sir1p binds the N-terminal region of Orc1p encompassing a Bromo-adjacent homology (BAH) domain found in various chromatin-associated proteins. To understand the molecular mechanism of Sir protein recruitment, we have determined a 2.5-A cocrystal structure of the N-terminal domain of Orc1p in complex with the Orc1p-interacting domain of Sir1p. The structure reveals that Sir1p Orc1p-interacting domain has a bilobal structure: an alpha/beta N-terminal lobe and a C-terminal lobe resembling the Tudor domain royal family fold. The N-terminal lobe of Sir1p binds in a shallow groove between a helical subdomain and the BAH domain of Orc1p. The structure provides a mechanistic understanding of Orc1p-Sir1p interaction specificity, as well as insights into protein-protein interactions involving BAH domains in general.

Pubmed ID: 15937111 RIS Download

Mesh terms: Amino Acid Sequence | Crystallography | DNA-Binding Proteins | Epigenesis, Genetic | Escherichia coli | Gene Silencing | Models, Molecular | Molecular Sequence Data | Origin Recognition Complex | Protein Binding | Protein Structure, Tertiary | Saccharomyces cerevisiae | Silent Information Regulator Proteins, Saccharomyces cerevisiae

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Associated grants

  • Agency: NCI NIH HHS, Id: CA13106
  • Agency: NIGMS NIH HHS, Id: GM 63716
  • Agency: NIGMS NIH HHS, Id: GM45436
  • Agency: NIGMS NIH HHS, Id: R01 GM045436

Mouse Genome Informatics (Data, Gene Annotation)

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