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| ==Crystal structure of Sir2 C543S mutant in complex with SID domain of Sir4== | | ==Crystal structure of Sir2 C543S mutant in complex with SID domain of Sir4== |
- | <StructureSection load='4iao' size='340' side='right' caption='[[4iao]], [[Resolution|resolution]] 2.90Å' scene=''> | + | <StructureSection load='4iao' size='340' side='right'caption='[[4iao]], [[Resolution|resolution]] 2.90Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
- | <table><tr><td colspan='2'>[[4iao]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Baker's_yeast Baker's yeast]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4IAO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4IAO FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4iao]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae_S288C Saccharomyces cerevisiae S288C]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4IAO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4IAO FirstGlance]. <br> |
- | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=APR:ADENOSINE-5-DIPHOSPHORIBOSE'>APR</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=APR:ADENOSINE-5-DIPHOSPHORIBOSE'>APR</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
- | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SIR2, MAR1, YDL042C, D2714 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=559292 Baker's yeast]), SIR4, ASD1, STE9, UTH2, YDR227W, YD9934.12 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=559292 Baker's yeast])</td></tr>
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4iao FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4iao OCA], [https://pdbe.org/4iao PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4iao RCSB], [https://www.ebi.ac.uk/pdbsum/4iao PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4iao ProSAT]</span></td></tr> |
- | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4iao FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4iao OCA], [http://pdbe.org/4iao PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4iao RCSB], [http://www.ebi.ac.uk/pdbsum/4iao PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4iao ProSAT]</span></td></tr> | + | |
| </table> | | </table> |
| == Function == | | == Function == |
- | [[http://www.uniprot.org/uniprot/SIR2_YEAST SIR2_YEAST]] NAD-dependent deacetylase, which participates in a wide range of cellular events including chromosome silencing, chromosome segregation, DNA recombination and the determination of life span. Involved in transcriptional repression of the silent mating-type loci HML and HMR and telomeric silencing via its association with SIR3 and SIR4. Plays a central role in ribosomal DNA (rDNA) silencing via its association with the RENT complex, preventing hyperrecombination, and repressing transcription from foreign promoters, which contributes to extending life span. Probably represses transcription via the formation of heterochromatin structure, which involves the compaction of chromatin fiber into a more condensed form, although this complex in at least one case can still bind euchromatic levels of positive transcription regulators. Although it displays some NAD-dependent histone deacetylase activity on histone H3K9Ac and H3K14Ac and histone H4K16Ac in vitro, such activity is unclear in vivo and may not be essential.<ref>PMID:10619427</ref> <ref>PMID:10693811</ref> <ref>PMID:9278054</ref> <ref>PMID:12923057</ref> <ref>PMID:15274642</ref> <ref>PMID:18086879</ref> <ref>PMID:19220062</ref> [[http://www.uniprot.org/uniprot/SIR4_YEAST SIR4_YEAST]] The proteins SIR1 through SIR4 are required for transcriptional repression of the silent mating type loci, HML and HMR. The proteins SIR2 through SIR4 repress mulitple loci by modulating chromatin structure. Involves the compaction of chromatin fiber into a more condensed form.<ref>PMID:18039933</ref> | + | [https://www.uniprot.org/uniprot/SIR2_YEAST SIR2_YEAST] NAD-dependent deacetylase, which participates in a wide range of cellular events including chromosome silencing, chromosome segregation, DNA recombination and the determination of life span. Involved in transcriptional repression of the silent mating-type loci HML and HMR and telomeric silencing via its association with SIR3 and SIR4. Plays a central role in ribosomal DNA (rDNA) silencing via its association with the RENT complex, preventing hyperrecombination, and repressing transcription from foreign promoters, which contributes to extending life span. Probably represses transcription via the formation of heterochromatin structure, which involves the compaction of chromatin fiber into a more condensed form, although this complex in at least one case can still bind euchromatic levels of positive transcription regulators. Although it displays some NAD-dependent histone deacetylase activity on histone H3K9Ac and H3K14Ac and histone H4K16Ac in vitro, such activity is unclear in vivo and may not be essential.<ref>PMID:10619427</ref> <ref>PMID:10693811</ref> <ref>PMID:9278054</ref> <ref>PMID:12923057</ref> <ref>PMID:15274642</ref> <ref>PMID:18086879</ref> <ref>PMID:19220062</ref> |
| <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| ==See Also== | | ==See Also== |
- | *[[Histone deacetylase|Histone deacetylase]] | + | *[[Histone deacetylase 3D structures|Histone deacetylase 3D structures]] |
| == References == | | == References == |
| <references/> | | <references/> |
| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |
- | [[Category: Baker's yeast]] | + | [[Category: Large Structures]] |
- | [[Category: Chen, Z]] | + | [[Category: Saccharomyces cerevisiae S288C]] |
- | [[Category: Hsu, H C]] | + | [[Category: Chen Z]] |
- | [[Category: Sternglanz, R]] | + | [[Category: Hsu HC]] |
- | [[Category: Wang, C L]] | + | [[Category: Sternglanz R]] |
- | [[Category: Wang, M]] | + | [[Category: Wang CL]] |
- | [[Category: Xu, R M]] | + | [[Category: Wang M]] |
- | [[Category: Yang, N]] | + | [[Category: Xu RM]] |
- | [[Category: Deacetylase]]
| + | [[Category: Yang N]] |
- | [[Category: Hydrolase-transcription complex]]
| + | |
- | [[Category: Nucleus]]
| + | |
- | [[Category: Protein complex]]
| + | |
- | [[Category: Sir2]]
| + | |
| Structural highlights
Function
SIR2_YEAST NAD-dependent deacetylase, which participates in a wide range of cellular events including chromosome silencing, chromosome segregation, DNA recombination and the determination of life span. Involved in transcriptional repression of the silent mating-type loci HML and HMR and telomeric silencing via its association with SIR3 and SIR4. Plays a central role in ribosomal DNA (rDNA) silencing via its association with the RENT complex, preventing hyperrecombination, and repressing transcription from foreign promoters, which contributes to extending life span. Probably represses transcription via the formation of heterochromatin structure, which involves the compaction of chromatin fiber into a more condensed form, although this complex in at least one case can still bind euchromatic levels of positive transcription regulators. Although it displays some NAD-dependent histone deacetylase activity on histone H3K9Ac and H3K14Ac and histone H4K16Ac in vitro, such activity is unclear in vivo and may not be essential.[1] [2] [3] [4] [5] [6] [7]
Publication Abstract from PubMed
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.
Structural basis for allosteric stimulation of Sir2 activity by Sir4 binding.,Hsu HC, Wang CL, Wang M, Yang N, Chen Z, Sternglanz R, Xu RM Genes Dev. 2013 Jan 1;27(1):64-73. doi: 10.1101/gad.208140.112. PMID:23307867[8]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Tanny JC, Dowd GJ, Huang J, Hilz H, Moazed D. An enzymatic activity in the yeast Sir2 protein that is essential for gene silencing. Cell. 1999 Dec 23;99(7):735-45. PMID:10619427
- ↑ Imai S, Armstrong CM, Kaeberlein M, Guarente L. Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase. Nature. 2000 Feb 17;403(6771):795-800. PMID:10693811 doi:http://dx.doi.org/10.1038/35001622
- ↑ Tsukamoto Y, Kato J, Ikeda H. Silencing factors participate in DNA repair and recombination in Saccharomyces cerevisiae. Nature. 1997 Aug 28;388(6645):900-3. PMID:9278054 doi:http://dx.doi.org/10.1038/42288
- ↑ Huang J, Moazed D. Association of the RENT complex with nontranscribed and coding regions of rDNA and a regional requirement for the replication fork block protein Fob1 in rDNA silencing. Genes Dev. 2003 Sep 1;17(17):2162-76. Epub 2003 Aug 15. PMID:12923057 doi:http://dx.doi.org/10.1101/gad.1108403
- ↑ Borra MT, Langer MR, Slama JT, Denu JM. Substrate specificity and kinetic mechanism of the Sir2 family of NAD+-dependent histone/protein deacetylases. Biochemistry. 2004 Aug 3;43(30):9877-87. PMID:15274642 doi:http://dx.doi.org/10.1021/bi049592e
- ↑ Darst RP, Garcia SN, Koch MR, Pillus L. Slx5 promotes transcriptional silencing and is required for robust growth in the absence of Sir2. Mol Cell Biol. 2008 Feb;28(4):1361-72. Epub 2007 Dec 17. PMID:18086879 doi:http://dx.doi.org/MCB.01291-07
- ↑ Du J, Jiang H, Lin H. Investigating the ADP-ribosyltransferase activity of sirtuins with NAD analogues and 32P-NAD. Biochemistry. 2009 Apr 7;48(13):2878-90. doi: 10.1021/bi802093g. PMID:19220062 doi:10.1021/bi802093g
- ↑ Hsu HC, Wang CL, Wang M, Yang N, Chen Z, Sternglanz R, Xu RM. Structural basis for allosteric stimulation of Sir2 activity by Sir4 binding. Genes Dev. 2013 Jan 1;27(1):64-73. doi: 10.1101/gad.208140.112. PMID:23307867 doi:http://dx.doi.org/10.1101/gad.208140.112
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