6mil: Difference between revisions
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The | ==Crystal structure of AF9 YEATS domain in complex with histone H3K9bu== | ||
<StructureSection load='6mil' size='340' side='right'caption='[[6mil]], [[Resolution|resolution]] 1.93Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6mil]] is a 4 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=6MIL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6MIL FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.93Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BTK:N~6~-BUTANOYL-L-LYSINE'>BTK</scene>, <scene name='pdbligand=MLI:MALONATE+ION'>MLI</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene></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=6mil FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6mil OCA], [https://pdbe.org/6mil PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6mil RCSB], [https://www.ebi.ac.uk/pdbsum/6mil PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6mil ProSAT]</span></td></tr> | |||
</table> | |||
== Disease == | |||
[https://www.uniprot.org/uniprot/AF9_HUMAN AF9_HUMAN] A chromosomal aberration involving MLLT3 is associated with acute leukemias. Translocation t(9;11)(p22;q23) with KMT2A/MLL1. The result is a rogue activator protein. | |||
== Function == | |||
[https://www.uniprot.org/uniprot/AF9_HUMAN AF9_HUMAN] Component of the super elongation complex (SEC), a complex required to increase the catalytic rate of RNA polymerase II transcription by suppressing transient pausing by the polymerase at multiple sites along the DNA.<ref>PMID:20159561</ref> <ref>PMID:20471948</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The YEATS domain has been identified as a reader of histone acylation and more recently emerged as a promising anti-cancer therapeutic target. Here, we detail the structural mechanisms for pi-pi-pi stacking involving the YEATS domains of yeast Taf14 and human AF9 and acylated histone H3 peptides and explore DNA-binding activities of these domains. Taf14-YEATS selects for crotonyllysine, forming pi stacking with both the crotonyl amide and the alkene moiety, whereas AF9-YEATS exhibits comparable affinities to saturated and unsaturated acyllysines, engaging them through pi stacking with the acyl amide. Importantly, AF9-YEATS is capable of binding to DNA, whereas Taf14-YEATS is not. Using a structure-guided approach, we engineered a mutant of Taf14-YEATS that engages crotonyllysine through the aromatic-aliphatic-aromatic pi stacking and shows high selectivity for the crotonyl H3K9 modification. Our findings shed light on the molecular principles underlying recognition of acyllysine marks and reveal a previously unidentified DNA-binding activity of AF9-YEATS. | |||
Structural insights into the pi-pi-pi stacking mechanism and DNA-binding activity of the YEATS domain.,Klein BJ, Vann KR, Andrews FH, Wang WW, Zhang J, Zhang Y, Beloglazkina AA, Mi W, Li Y, Li H, Shi X, Kutateladze AG, Strahl BD, Liu WR, Kutateladze TG Nat Commun. 2018 Nov 1;9(1):4574. doi: 10.1038/s41467-018-07072-6. PMID:30385749<ref>PMID:30385749</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 6mil" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Histone 3D structures|Histone 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Klein BJ]] | |||
[[Category: Kutateladze TG]] | |||
[[Category: Vann KR]] | |||
Latest revision as of 09:32, 11 October 2023
Crystal structure of AF9 YEATS domain in complex with histone H3K9buCrystal structure of AF9 YEATS domain in complex with histone H3K9bu
Structural highlights
DiseaseAF9_HUMAN A chromosomal aberration involving MLLT3 is associated with acute leukemias. Translocation t(9;11)(p22;q23) with KMT2A/MLL1. The result is a rogue activator protein. FunctionAF9_HUMAN Component of the super elongation complex (SEC), a complex required to increase the catalytic rate of RNA polymerase II transcription by suppressing transient pausing by the polymerase at multiple sites along the DNA.[1] [2] Publication Abstract from PubMedThe YEATS domain has been identified as a reader of histone acylation and more recently emerged as a promising anti-cancer therapeutic target. Here, we detail the structural mechanisms for pi-pi-pi stacking involving the YEATS domains of yeast Taf14 and human AF9 and acylated histone H3 peptides and explore DNA-binding activities of these domains. Taf14-YEATS selects for crotonyllysine, forming pi stacking with both the crotonyl amide and the alkene moiety, whereas AF9-YEATS exhibits comparable affinities to saturated and unsaturated acyllysines, engaging them through pi stacking with the acyl amide. Importantly, AF9-YEATS is capable of binding to DNA, whereas Taf14-YEATS is not. Using a structure-guided approach, we engineered a mutant of Taf14-YEATS that engages crotonyllysine through the aromatic-aliphatic-aromatic pi stacking and shows high selectivity for the crotonyl H3K9 modification. Our findings shed light on the molecular principles underlying recognition of acyllysine marks and reveal a previously unidentified DNA-binding activity of AF9-YEATS. Structural insights into the pi-pi-pi stacking mechanism and DNA-binding activity of the YEATS domain.,Klein BJ, Vann KR, Andrews FH, Wang WW, Zhang J, Zhang Y, Beloglazkina AA, Mi W, Li Y, Li H, Shi X, Kutateladze AG, Strahl BD, Liu WR, Kutateladze TG Nat Commun. 2018 Nov 1;9(1):4574. doi: 10.1038/s41467-018-07072-6. PMID:30385749[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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