Hsu, H. C., Wang, C. L., Wang, M., Yang, N., Chen, Z., Sternglanz, R., Xu, R. M. (January 2013) Structural basis for allosteric stimulation of Sir2 activity by sir4 binding. Genes and Development, 27 (1). pp. 64-73. ISSN 08909369
Abstract
The budding yeast Sir2 (silent information regulator 2) protein is the founding member of the sirtuin family of NAD-dependent histone/protein deacetylases. Its function in transcriptional silencing requires both the highly conserved catalytic domain and a poorly understood N-terminal regulatory domain (Sir2N). We determined the structure of Sir2 in complex with a fragment of Sir4, a component of the transcriptional silencing complex in Saccharomyces cerevisiae. The structure shows that Sir4 is anchored to Sir2N and contacts the interface between the Sir2N and the catalytic domains through a long loop. We discovered that the interaction between the Sir4 loop and the interdomain interface in Sir2 is critical for allosteric stimulation of the deacetylase activity of Sir2. These results bring to light the structure and function of the regulatory domain of Sir2, and the knowledge should be useful for understanding allosteric regulation of sirtuins in general.
| Item Type: | Paper |
|---|---|
| Subjects: | bioinformatics > genomics and proteomics > genetics & nucleic acid processing bioinformatics > genomics and proteomics bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes > histone deacetylase bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types organism description > yeast |
| CSHL Authors: | |
| Communities: | CSHL labs > Van Aelst lab |
| Depositing User: | Matt Covey |
| Date: | 1 January 2013 |
| Date Deposited: | 11 Feb 2013 17:05 |
| Last Modified: | 22 Oct 2025 15:22 |
| PMCID: | PMC3553284 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/27237 |
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