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

Hsu, H. C., Stillman, B., Xu, R. M. (June 2005) Structural basis for origin recognition complex 1 protein-silence information regulator 1 protein interaction in epigenetic silencing. Proc Natl Acad Sci U S A, 102 (24). pp. 8519-24. ISSN 0027-8424 (Print)

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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.

Item Type:	Paper
Uncontrolled Keywords:	Amino Acid Sequence Crystallography DNA-Binding Proteins genetics metabolism Epigenesis Genetic Escherichia coli Gene Silencing Models Molecular Molecular Sequence Data Origin Recognition Complex Protein Binding Protein Structure, Tertiary Saccharomyces cerevisiae genetics metabolism Silent Information Regulator Proteins Saccharomyces cerevisiae genetics metabolism
Subjects:	bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > transcription bioinformatics > genomics and proteomics > genetics & nucleic acid processing bioinformatics > genomics and proteomics bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification organism description > yeast > Saccharomyces bioinformatics > genomics and proteomics > genetics & nucleic acid processing > epigenetics bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > epigenetics bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > gene silencing bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > origin recognition complex bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types Investigative techniques and equipment > x ray crystallography
CSHL Authors:	Hsu, Hao-Chi Stillman, Bruce W. Xu, Rui-Ming
Communities:	CSHL labs > Stillman lab
Highlight:	Stillman, Bruce W.
Depositing User:	CSHL Librarian
Date:	14 June 2005
Date Deposited:	12 Jan 2012 20:17
Last Modified:	09 Nov 2017 16:43
PMCID:	PMC1150838
Related URLs:	Publisher
URI:	https://repository.cshl.edu/id/eprint/22600

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