Structural basis for origin recognition complex 1 protein-silence information regulator 1 protein interaction in epigenetic silencing.
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.
Hsu
Hao-Chi
HC
Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
Stillman
Bruce
B
Xu
Rui-Ming
RM
D000595:Amino Acid Sequence; D003461:Crystallography; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D044127:Epigenesis, Genetic; D004926:Escherichia coli; D020868:Gene Silencing; D008958:Models, Molecular; D008969:Molecular Sequence Data; D051738:Origin Recognition Complex; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*
D004268:DNA-Binding Proteins; D051738:Origin Recognition Complex; C084121:SIR1 protein, S cerevisiae; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae