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| | ==Chromodomain HP1 with a p-nitro-L-phenylalanine mutation at position 24 bound to histone H3 peptide containing trimethyl lysine== | | ==Chromodomain HP1 with a p-nitro-L-phenylalanine mutation at position 24 bound to histone H3 peptide containing trimethyl lysine== |
| - | <StructureSection load='6at0' size='340' side='right' caption='[[6at0]], [[Resolution|resolution]] 1.28Å' scene=''> | + | <StructureSection load='6at0' size='340' side='right'caption='[[6at0]], [[Resolution|resolution]] 1.28Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6at0]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Drome Drome]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6AT0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6AT0 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6at0]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Drosophila_melanogaster Drosophila melanogaster]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6AT0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6AT0 FirstGlance]. <br> |
| - | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=M3L:N-TRIMETHYLLYSINE'>M3L</scene>, <scene name='pdbligand=PPN:PARA-NITROPHENYLALANINE'>PPN</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]] 1.285Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Su(var)205, HP1, CG8409 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=7227 DROME])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=M3L:N-TRIMETHYLLYSINE'>M3L</scene>, <scene name='pdbligand=PPN:PARA-NITROPHENYLALANINE'>PPN</scene></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=6at0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6at0 OCA], [http://pdbe.org/6at0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6at0 RCSB], [http://www.ebi.ac.uk/pdbsum/6at0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6at0 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=6at0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6at0 OCA], [https://pdbe.org/6at0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6at0 RCSB], [https://www.ebi.ac.uk/pdbsum/6at0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6at0 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/HP1_DROME HP1_DROME]] Structural component of heterochromatin, involved in gene repression and the modification of position-effect-variegation. Recognizes and binds histone H3 tails methylated at 'Lys-9', leading to epigenetic repression. | + | [https://www.uniprot.org/uniprot/HP1_DROME HP1_DROME] Structural component of heterochromatin, involved in gene repression and the modification of position-effect-variegation. Recognizes and binds histone H3 tails methylated at 'Lys-9', leading to epigenetic repression. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Drome]] | + | [[Category: Drosophila melanogaster]] |
| - | [[Category: Baril, S A]] | + | [[Category: Large Structures]] |
| - | [[Category: Brustad, E M]] | + | [[Category: Baril SA]] |
| - | [[Category: Waters, M L]] | + | [[Category: Brustad EM]] |
| - | [[Category: Histone reader]] | + | [[Category: Waters ML]] |
| - | [[Category: Transcription]]
| + | |
| Structural highlights
Function
HP1_DROME Structural component of heterochromatin, involved in gene repression and the modification of position-effect-variegation. Recognizes and binds histone H3 tails methylated at 'Lys-9', leading to epigenetic repression.
Publication Abstract from PubMed
Trimethyllysine (Kme3) reader proteins are targets for inhibition due to their role in mediating gene expression. Although all such reader proteins bind Kme3 in an aromatic cage, the driving force for binding may differ; some readers exhibit evidence for cation-pi interactions whereas others do not. We report a general unnatural amino acid mutagenesis approach to quantify the contribution of individual tyrosines to cation binding using the HP1 chromodomain as a model system. We demonstrate that two tyrosines (Y24 and Y48) bind to a Kme3-histone tail peptide via cation-pi interactions, but linear free energy trends suggest they do not contribute equally to binding. X-ray structures and computational analysis suggest that the distance and degree of contact between Tyr residues and Kme3 plays an important role in tuning cation-pi-mediated Kme3 recognition. Although cation-pi interactions have been studied in a number of proteins, this work is the first to utilize direct binding assays, X-ray crystallography, and modeling, to pinpoint factors that influence the magnitude of the individual cation-pi interactions.
Investigation of Trimethyllysine Binding by the HP1 Chromodomain via Unnatural Amino Acid Mutagenesis.,Baril SA, Koenig AL, Krone MW, Albanese KI, He CQ, Lee GY, Houk KN, Waters ML, Brustad EM J Am Chem Soc. 2017 Nov 20. doi: 10.1021/jacs.7b09223. PMID:29111699[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Baril SA, Koenig AL, Krone MW, Albanese KI, He CQ, Lee GY, Houk KN, Waters ML, Brustad EM. Investigation of Trimethyllysine Binding by the HP1 Chromodomain via Unnatural Amino Acid Mutagenesis. J Am Chem Soc. 2017 Nov 20. doi: 10.1021/jacs.7b09223. PMID:29111699 doi:http://dx.doi.org/10.1021/jacs.7b09223
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