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| | <StructureSection load='6cw2' size='340' side='right'caption='[[6cw2]], [[Resolution|resolution]] 2.67Å' scene=''> | | <StructureSection load='6cw2' size='340' side='right'caption='[[6cw2]], [[Resolution|resolution]] 2.67Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6cw2]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Atcc_18824 Atcc 18824], [http://en.wikipedia.org/wiki/Baker's_yeast Baker's yeast] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6CW2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6CW2 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6cw2]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens], [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae] and [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=6CW2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6CW2 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.67Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">GCN5, ADA4, SWI9, YGR252W ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=559292 Baker's yeast]), ADA2, SCKG_0090 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=4932 ATCC 18824])</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Histone_acetyltransferase Histone acetyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.1.48 2.3.1.48] </span></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=6cw2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6cw2 OCA], [https://pdbe.org/6cw2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6cw2 RCSB], [https://www.ebi.ac.uk/pdbsum/6cw2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6cw2 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=6cw2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6cw2 OCA], [http://pdbe.org/6cw2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6cw2 RCSB], [http://www.ebi.ac.uk/pdbsum/6cw2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6cw2 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/GCN5_YEAST GCN5_YEAST]] Acetylates histone H2B to form H2BK11ac and H2BK16ac, histone H3 to form H3K9ac, H3K14ac, H3K18ac, H3K23ac, H3K27ac and H3K36ac, with a lower preference histone H4 to form H4K8ac and H4K16ac, and contributes to H2A.Z acetylation. Acetylation of histones gives a specific tag for epigenetic transcription activation. Operates in concert with certain DNA-binding transcriptional activators such as GCN4 or HAP2/3/4. Its acetyltransferase activity seems to be dependent on the association in different multisubunit complexes. Functions as histone acetyltransferase component of the transcription regulatory histone acetylation (HAT) complexes SAGA, SALSA and ADA. SAGA is involved in RNA polymerase II-dependent transcriptional regulation of approximately 10% of yeast genes. At the promoters, SAGA is required for recruitment of the basal transcription machinery. It influences RNA polymerase II transcriptional activity through different activities such as TBP interaction (SPT3, SPT8 and SPT20) and promoter selectivity, interaction with transcription activators (GCN5, ADA2, ADA3 and TRA1), and chromatin modification through histone acetylation (GCN5) and deubiquitination (UBP8). SAGA acetylates nucleosomal histone H3 to some extent (to form H3K9ac, H3K14ac, H3K18ac and H3K23ac). SAGA interacts with DNA via upstream activating sequences (UASs). SALSA, an altered form of SAGA, may be involved in positive transcriptional regulation. The ADA histone acetyltransferase complex preferentially acetylates nucleosomal histones H3 (to form H3K14ac and H3K18ac) and H2B, leading to transcription regulation. SLIK is proposed to have partly overlapping functions with SAGA. It preferentially acetylates methylated histone H3, at least after activation at the GAL1-10 locus.<ref>PMID:10026213</ref> <ref>PMID:16543222</ref> <ref>PMID:16543223</ref> | + | [https://www.uniprot.org/uniprot/GCN5_YEAST GCN5_YEAST] Acetylates histone H2B to form H2BK11ac and H2BK16ac, histone H3 to form H3K9ac, H3K14ac, H3K18ac, H3K23ac, H3K27ac and H3K36ac, with a lower preference histone H4 to form H4K8ac and H4K16ac, and contributes to H2A.Z acetylation. Acetylation of histones gives a specific tag for epigenetic transcription activation. Operates in concert with certain DNA-binding transcriptional activators such as GCN4 or HAP2/3/4. Its acetyltransferase activity seems to be dependent on the association in different multisubunit complexes. Functions as histone acetyltransferase component of the transcription regulatory histone acetylation (HAT) complexes SAGA, SALSA and ADA. SAGA is involved in RNA polymerase II-dependent transcriptional regulation of approximately 10% of yeast genes. At the promoters, SAGA is required for recruitment of the basal transcription machinery. It influences RNA polymerase II transcriptional activity through different activities such as TBP interaction (SPT3, SPT8 and SPT20) and promoter selectivity, interaction with transcription activators (GCN5, ADA2, ADA3 and TRA1), and chromatin modification through histone acetylation (GCN5) and deubiquitination (UBP8). SAGA acetylates nucleosomal histone H3 to some extent (to form H3K9ac, H3K14ac, H3K18ac and H3K23ac). SAGA interacts with DNA via upstream activating sequences (UASs). SALSA, an altered form of SAGA, may be involved in positive transcriptional regulation. The ADA histone acetyltransferase complex preferentially acetylates nucleosomal histones H3 (to form H3K14ac and H3K18ac) and H2B, leading to transcription regulation. SLIK is proposed to have partly overlapping functions with SAGA. It preferentially acetylates methylated histone H3, at least after activation at the GAL1-10 locus.<ref>PMID:10026213</ref> <ref>PMID:16543222</ref> <ref>PMID:16543223</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | *[[Antibody 3D structures|Antibody 3D structures]] | | *[[Antibody 3D structures|Antibody 3D structures]] |
| | *[[Histone acetyltransferase 3D structures|Histone acetyltransferase 3D structures]] | | *[[Histone acetyltransferase 3D structures|Histone acetyltransferase 3D structures]] |
| | + | *[[3D structures of human antibody|3D structures of human antibody]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Atcc 18824]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Baker's yeast]]
| + | |
| - | [[Category: Histone acetyltransferase]]
| + | |
| - | [[Category: Human]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Barrios, A F]] | + | [[Category: Saccharomyces cerevisiae]] |
| - | [[Category: Kim, S A]] | + | [[Category: Saccharomyces cerevisiae S288C]] |
| - | [[Category: Kossiakoff, A A]] | + | [[Category: Barrios AF]] |
| - | [[Category: Kramer, R M]] | + | [[Category: Kim SA]] |
| - | [[Category: Lu, V]] | + | [[Category: Kossiakoff AA]] |
| - | [[Category: Luke, J]] | + | [[Category: Kramer RM]] |
| - | [[Category: Paduch, M]] | + | [[Category: Lu V]] |
| - | [[Category: Sun, J]] | + | [[Category: Luke J]] |
| - | [[Category: Tan, S]] | + | [[Category: Paduch M]] |
| - | [[Category: Usatyuk, S]] | + | [[Category: Sun J]] |
| - | [[Category: Ada2/gcn5 structure]]
| + | [[Category: Tan S]] |
| - | [[Category: Gene regulation]]
| + | [[Category: Usatyuk S]] |
| Structural highlights
Function
GCN5_YEAST Acetylates histone H2B to form H2BK11ac and H2BK16ac, histone H3 to form H3K9ac, H3K14ac, H3K18ac, H3K23ac, H3K27ac and H3K36ac, with a lower preference histone H4 to form H4K8ac and H4K16ac, and contributes to H2A.Z acetylation. Acetylation of histones gives a specific tag for epigenetic transcription activation. Operates in concert with certain DNA-binding transcriptional activators such as GCN4 or HAP2/3/4. Its acetyltransferase activity seems to be dependent on the association in different multisubunit complexes. Functions as histone acetyltransferase component of the transcription regulatory histone acetylation (HAT) complexes SAGA, SALSA and ADA. SAGA is involved in RNA polymerase II-dependent transcriptional regulation of approximately 10% of yeast genes. At the promoters, SAGA is required for recruitment of the basal transcription machinery. It influences RNA polymerase II transcriptional activity through different activities such as TBP interaction (SPT3, SPT8 and SPT20) and promoter selectivity, interaction with transcription activators (GCN5, ADA2, ADA3 and TRA1), and chromatin modification through histone acetylation (GCN5) and deubiquitination (UBP8). SAGA acetylates nucleosomal histone H3 to some extent (to form H3K9ac, H3K14ac, H3K18ac and H3K23ac). SAGA interacts with DNA via upstream activating sequences (UASs). SALSA, an altered form of SAGA, may be involved in positive transcriptional regulation. The ADA histone acetyltransferase complex preferentially acetylates nucleosomal histones H3 (to form H3K14ac and H3K18ac) and H2B, leading to transcription regulation. SLIK is proposed to have partly overlapping functions with SAGA. It preferentially acetylates methylated histone H3, at least after activation at the GAL1-10 locus.[1] [2] [3]
Publication Abstract from PubMed
The Gcn5 histone acetyltransferase (HAT) subunit of the SAGA transcriptional coactivator complex catalyzes acetylation of histone H3 and H2B N-terminal tails, posttranslational modifications associated with gene activation. Binding of the SAGA subunit partner Ada2 to Gcn5 activates Gcn5's intrinsically weak HAT activity on histone proteins, but the mechanism for this activation by the Ada2 SANT domain has remained elusive. We have employed Fab antibody fragments as crystallization chaperones to determine crystal structures of a yeast Ada2/Gcn5 complex. Our structural and biochemical results indicate that the Ada2 SANT domain does not activate Gcn5's activity by directly affecting histone peptide binding as previously proposed. Instead, the Ada2 SANT domain enhances Gcn5 binding of the enzymatic cosubstrate acetyl-CoA. This finding suggests a mechanism for regulating chromatin modification enzyme activity: controlling binding of the modification cosubstrate instead of the histone substrate.
Structural basis for activation of SAGA histone acetyltransferase Gcn5 by partner subunit Ada2.,Sun J, Paduch M, Kim SA, Kramer RM, Barrios AF, Lu V, Luke J, Usatyuk S, Kossiakoff AA, Tan S Proc Natl Acad Sci U S A. 2018 Sep 17. pii: 1805343115. doi:, 10.1073/pnas.1805343115. PMID:30224453[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Grant PA, Eberharter A, John S, Cook RG, Turner BM, Workman JL. Expanded lysine acetylation specificity of Gcn5 in native complexes. J Biol Chem. 1999 Feb 26;274(9):5895-900. PMID:10026213
- ↑ Babiarz JE, Halley JE, Rine J. Telomeric heterochromatin boundaries require NuA4-dependent acetylation of histone variant H2A.Z in Saccharomyces cerevisiae. Genes Dev. 2006 Mar 15;20(6):700-10. PMID:16543222 doi:http://dx.doi.org/10.1101/gad.1386306
- ↑ Millar CB, Xu F, Zhang K, Grunstein M. Acetylation of H2AZ Lys 14 is associated with genome-wide gene activity in yeast. Genes Dev. 2006 Mar 15;20(6):711-22. PMID:16543223 doi:http://dx.doi.org/20/6/711
- ↑ Sun J, Paduch M, Kim SA, Kramer RM, Barrios AF, Lu V, Luke J, Usatyuk S, Kossiakoff AA, Tan S. Structural basis for activation of SAGA histone acetyltransferase Gcn5 by partner subunit Ada2. Proc Natl Acad Sci U S A. 2018 Sep 17. pii: 1805343115. doi:, 10.1073/pnas.1805343115. PMID:30224453 doi:http://dx.doi.org/10.1073/pnas.1805343115
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