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==Crystal structure of MOZ double PHD finger mutant-S210D/N235R in complex with histone H3 crotonylation at K14== | ==Crystal structure of MOZ double PHD finger mutant-S210D/N235R in complex with histone H3 crotonylation at K14== | ||
<StructureSection load='5b78' size='340' side='right' caption='[[5b78]], [[Resolution|resolution]] 1.40Å' scene=''> | <StructureSection load='5b78' size='340' side='right'caption='[[5b78]], [[Resolution|resolution]] 1.40Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5b78]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5B78 OCA]. For a <b>guided tour on the structure components</b> use [ | <table><tr><td colspan='2'>[[5b78]] is a 2 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=5B78 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5B78 FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.4Å</td></tr> | ||
<tr id=' | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=KCR:N-6-CROTONYL-L-LYSINE'>KCR</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'>[https://proteopedia.org/fgij/fg.htm?mol=5b78 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5b78 OCA], [https://pdbe.org/5b78 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5b78 RCSB], [https://www.ebi.ac.uk/pdbsum/5b78 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5b78 ProSAT]</span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Disease == | == Disease == | ||
[ | [https://www.uniprot.org/uniprot/KAT6A_HUMAN KAT6A_HUMAN] Note=Chromosomal aberrations involving KAT6A may be a cause of acute myeloid leukemias. Translocation t(8;16)(p11;p13) with CREBBP; translocation t(8;22)(p11;q13) with EP300. KAT6A-CREBBP may induce leukemia by inhibiting RUNX1-mediated transcription. Inversion inv(8)(p11;q13) generates the KAT6A-NCOA2 oncogene, which consists of the N-terminal part of KAT6A and the C-terminal part of NCOA2/TIF2. KAT6A-NCOA2 binds to CREBBP and disrupts its function in transcription activation. Note=A chromosomal aberration involving KAT6A is a cause of therapy-related myelodysplastic syndrome. Translocation t(2;8)(p23;p11.2) with ASXL2 generates a KAT6A-ASXL2 fusion protein. | ||
== Function == | == Function == | ||
[ | [https://www.uniprot.org/uniprot/KAT6A_HUMAN KAT6A_HUMAN] Histone acetyltransferase that acetylates lysine residues in histone H3 and histone H4 (in vitro). Component of the MOZ/MORF complex which has a histone H3 acetyltransferase activity. May act as a transcriptional coactivator for RUNX1 and RUNX2.<ref>PMID:11742995</ref> <ref>PMID:11965546</ref> <ref>PMID:12771199</ref> <ref>PMID:16387653</ref> <ref>PMID:17925393</ref> | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Recognition of histone covalent modifications by 'reader' modules constitutes a major mechanism for epigenetic regulation. A recent upsurge of newly discovered histone lysine acylations, such as crotonylation (Kcr), butyrylation (Kbu), and propionylation (Kpr), greatly expands the coding potential of histone lysine modifications. Here we demonstrate that the histone acetylation-binding double PHD finger (DPF) domains of human MOZ (also known as KAT6A) and DPF2 (also known as BAF45d) accommodate a wide range of histone lysine acylations with the strongest preference for Kcr. Crystal structures of the DPF domain of MOZ in complex with H3K14cr, H3K14bu, and H3K14pr peptides reveal that these non-acetyl acylations are anchored in a hydrophobic 'dead-end' pocket with selectivity for crotonylation arising from intimate encapsulation and an amide-sensing hydrogen bonding network. Immunofluorescence and chromatin immunoprecipitation (ChIP)-quantitative PCR (qPCR) showed that MOZ and H3K14cr colocalize in a DPF-dependent manner. Our studies call attention to a new regulatory mechanism centered on histone crotonylation readout by DPF family members. | |||
Selective recognition of histone crotonylation by double PHD fingers of MOZ and DPF2.,Xiong X, Panchenko T, Yang S, Zhao S, Yan P, Zhang W, Xie W, Li Y, Zhao Y, Allis CD, Li H Nat Chem Biol. 2016 Dec;12(12):1111-1118. doi: 10.1038/nchembio.2218. Epub 2016, Oct 24. PMID:27775714<ref>PMID:27775714</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 5b78" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Histone acetyltransferase 3D structures|Histone acetyltransferase 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Li H]] | ||
[[Category: | [[Category: Xiong X]] | ||
Latest revision as of 19:02, 8 November 2023
Crystal structure of MOZ double PHD finger mutant-S210D/N235R in complex with histone H3 crotonylation at K14Crystal structure of MOZ double PHD finger mutant-S210D/N235R in complex with histone H3 crotonylation at K14
Structural highlights
DiseaseKAT6A_HUMAN Note=Chromosomal aberrations involving KAT6A may be a cause of acute myeloid leukemias. Translocation t(8;16)(p11;p13) with CREBBP; translocation t(8;22)(p11;q13) with EP300. KAT6A-CREBBP may induce leukemia by inhibiting RUNX1-mediated transcription. Inversion inv(8)(p11;q13) generates the KAT6A-NCOA2 oncogene, which consists of the N-terminal part of KAT6A and the C-terminal part of NCOA2/TIF2. KAT6A-NCOA2 binds to CREBBP and disrupts its function in transcription activation. Note=A chromosomal aberration involving KAT6A is a cause of therapy-related myelodysplastic syndrome. Translocation t(2;8)(p23;p11.2) with ASXL2 generates a KAT6A-ASXL2 fusion protein. FunctionKAT6A_HUMAN Histone acetyltransferase that acetylates lysine residues in histone H3 and histone H4 (in vitro). Component of the MOZ/MORF complex which has a histone H3 acetyltransferase activity. May act as a transcriptional coactivator for RUNX1 and RUNX2.[1] [2] [3] [4] [5] Publication Abstract from PubMedRecognition of histone covalent modifications by 'reader' modules constitutes a major mechanism for epigenetic regulation. A recent upsurge of newly discovered histone lysine acylations, such as crotonylation (Kcr), butyrylation (Kbu), and propionylation (Kpr), greatly expands the coding potential of histone lysine modifications. Here we demonstrate that the histone acetylation-binding double PHD finger (DPF) domains of human MOZ (also known as KAT6A) and DPF2 (also known as BAF45d) accommodate a wide range of histone lysine acylations with the strongest preference for Kcr. Crystal structures of the DPF domain of MOZ in complex with H3K14cr, H3K14bu, and H3K14pr peptides reveal that these non-acetyl acylations are anchored in a hydrophobic 'dead-end' pocket with selectivity for crotonylation arising from intimate encapsulation and an amide-sensing hydrogen bonding network. Immunofluorescence and chromatin immunoprecipitation (ChIP)-quantitative PCR (qPCR) showed that MOZ and H3K14cr colocalize in a DPF-dependent manner. Our studies call attention to a new regulatory mechanism centered on histone crotonylation readout by DPF family members. Selective recognition of histone crotonylation by double PHD fingers of MOZ and DPF2.,Xiong X, Panchenko T, Yang S, Zhao S, Yan P, Zhang W, Xie W, Li Y, Zhao Y, Allis CD, Li H Nat Chem Biol. 2016 Dec;12(12):1111-1118. doi: 10.1038/nchembio.2218. Epub 2016, Oct 24. PMID:27775714[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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