|
|
| Line 3: |
Line 3: |
| | <StructureSection load='5t8r' size='340' side='right'caption='[[5t8r]], [[Resolution|resolution]] 2.40Å' scene=''> | | <StructureSection load='5t8r' size='340' side='right'caption='[[5t8r]], [[Resolution|resolution]] 2.40Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5t8r]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5T8R OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5T8R FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5t8r]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5T8R OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5T8R FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <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]] 2.4Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BAZ2A, KIAA0314, TIP5 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5t8r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5t8r OCA], [http://pdbe.org/5t8r PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5t8r RCSB], [http://www.ebi.ac.uk/pdbsum/5t8r PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5t8r ProSAT]</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=5t8r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5t8r OCA], [https://pdbe.org/5t8r PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5t8r RCSB], [https://www.ebi.ac.uk/pdbsum/5t8r PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5t8r ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/BAZ2A_HUMAN BAZ2A_HUMAN]] Essential component of the NoRC (nucleolar remodeling complex) complex, a complex that mediates silencing of a fraction of rDNA by recruiting histone-modifying enzymes and DNA methyltransferases, leading to heterochromatin formation and transcriptional silencing. In the complex, it plays a central role by being recruited to rDNA and by targeting chromatin modifying enzymes such as HDAC1, leading to repress RNA polymerase I transcription. Recruited to rDNA via its interaction with TTF1 and its ability to recognize and bind histone H4 acetylated on 'Lys-16' (H4K16ac), leading to deacetylation of H4K5ac, H4K8ac, H4K12ac but not H4K16ac. Specifically binds pRNAs, 150-250 nucleotide RNAs that are complementary in sequence to the rDNA promoter; pRNA-binding is required for heterochromatin formation and rDNA silencing (By similarity). | + | [https://www.uniprot.org/uniprot/H31_HUMAN H31_HUMAN] |
| - | <div style="background-color:#fffaf0;">
| + | |
| - | == Publication Abstract from PubMed ==
| + | |
| - | The plant homeodomain (PHD) fingers are amongst the largest family of epigenetic domains, first characterized as readers of methylated H3K4. Readout of histone post-translational modifications by PHDs has been the subject of intense investigation, however less is known about the recognition of secondary structure features within histone tail itself. We solved the crystal structure of the PHD finger of the bromodomain adjacent to zinc finger 2A (BAZ2A, also known as TIP5) in complex with unmodified N-terminal histone H3 tail. The peptide is bound in a helical folded-back conformation after K4, induced by an acidic patch on the protein surface that prevents peptide binding in an extended conformation. Structural bioinformatics analyses identify a conserved Asp/Glu residue that we name "acidic wall", found to be mutually exclusive with the conserved Trp for K4Me recognition. Neutralization or inversion of the charges at the acidic wall patch in BAZ2A, and homologous BAZ2B, weakened H3 binding. We identify simple mutations on H3 that strikingly enhance or reduce binding, as a result of their stabilization or de-stabilization of H3 helicity. Our work unravels the structural basis for binding of helical H3 tail by PHD fingers, and suggests that molecular recognition of secondary structure motifs within histone tails could represent an additional layer of regulation in epigenetic processes.
| + | |
| - | | + | |
| - | Structural Basis of Molecular Recognition of Helical Histone H3 Tail by PHD Finger Domains.,Bortoluzzi A, Amato A, Lucas X, Blank M, Ciulli A Biochem J. 2017 Apr 3. pii: BCJ20161053. doi: 10.1042/BCJ20161053. PMID:28341809<ref>PMID:28341809</ref>
| + | |
| - | | + | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 5t8r" style="background-color:#fffaf0;"></div>
| + | |
| | | | |
| | ==See Also== | | ==See Also== |
| | *[[Bromodomain adjacent to zinc finger 3D structures|Bromodomain adjacent to zinc finger 3D structures]] | | *[[Bromodomain adjacent to zinc finger 3D structures|Bromodomain adjacent to zinc finger 3D structures]] |
| - | == References == | |
| - | <references/> | |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Amato, A]] | + | [[Category: Amato A]] |
| - | [[Category: Bortoluzzi, A]] | + | [[Category: Bortoluzzi A]] |
| - | [[Category: Ciulli, A]] | + | [[Category: Ciulli A]] |
| - | [[Category: Gadd, M S]] | + | [[Category: Gadd MS]] |
| - | [[Category: Complex]]
| + | |
| - | [[Category: Histone3]]
| + | |
| - | [[Category: Phd zinc finger]]
| + | |
| - | [[Category: Transcription]]
| + | |
