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

Proc Natl Acad Sci U S A. 2005 Jun 14;102(24):8519-24. doi: 10.1073/pnas.0502946102. Epub 2005 Jun 3.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Crystallography
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism*
  • Epigenesis, Genetic*
  • Escherichia coli
  • Gene Silencing*
  • Models, Molecular*
  • Molecular Sequence Data
  • Origin Recognition Complex
  • Protein Binding
  • Protein Structure, Tertiary
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism*
  • Silent Information Regulator Proteins, Saccharomyces cerevisiae / genetics
  • Silent Information Regulator Proteins, Saccharomyces cerevisiae / metabolism*

Substances

  • DNA-Binding Proteins
  • Origin Recognition Complex
  • SIR1 protein, S cerevisiae
  • Silent Information Regulator Proteins, Saccharomyces cerevisiae

Associated data

  • PDB/1ZBX