Structure of the Sir3 protein bromo adjacent homology (BAH) domain from S. cerevisiae at 1.95 A resolution.
Sir3p is a silent-information-regulator (SIR) protein required for the assembly of a transcriptionally "silent" chromatin structure at telomeres and the cryptic HM mating-type loci in Saccharomyces cerevisiae. Sir3p contains a putative "bromo adjacent homology" (BAH) domain at its N terminus that shares strong sequence similarity with the BAH domain of a subunit of the origin recognition complex (ORC), Orc1p. The Orc1p-BAH domain forms a well-defined complex with the ORC interaction region (OIR) of another Sir protein, Sir1p, which targets formation of silent chromatin to the HM-loci. Interestingly, despite sequence similarity of the Sir3p and Orc1p BAH domains and Sir3p's established importance in silencing, Sir3p does not bind the Sir1p-OIR. Here we report the 1.95 A resolution crystal structure of the Sir3p-BAH domain. The structure reveals two key features that can account for Sir3p-BAH domain's inability to interact with Sir1p. First, several Orc1p-BAH domain residues known to directly contact Sir1p are altered in the Sir3p-BAH domain. Second, a critical OIR-binding pocket present on the surface of the Orc1p-BAH domain is "filled" in the Sir3p-BAH domain structure, potentially making it inaccessible to Sir1p. These findings imply that the Sir3p-BAH domain structure has evolved for functions distinct from those of the Orc1p-BAH domain.
Hou
Zhonggang
Z
Department of Biomolecular Chemistry, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin 53706-1532, USA.
Danzer
John R
JR
Fox
Catherine A
CA
Keck
James L
JL
D000595:Amino Acid Sequence; D015966:Gene Expression Regulation, Fungal; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae / Q000737:chemistry*; D013329:Structure-Activity Relationship
D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae