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2qic

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Revision as of 11:27, 5 September 2018

Crystal Structure of the ING1 PHD Finger in complex with a Histone H3K4ME3 peptide

Structural highlights

2qic is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
NonStd Res:
Gene:	ING1 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[ING1_HUMAN] Defects in ING1 are a cause of head and neck squamous cell carcinomas (HNSCC) [MIM:275355]; also known as squamous cell carcinoma of the head and neck.^[1]

Function

[ING1_HUMAN] Cooperates with p53/TP53 in the negative regulatory pathway of cell growth by modulating p53-dependent transcriptional activation. Implicated as a tumor suppressor gene.^[2]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Inhibitor of growth 1 (ING1) is implicated in oncogenesis, DNA damage repair, and apoptosis. Mutations within the ING1 gene and altered expression levels of ING1 are found in multiple human cancers. Here, we show that both DNA repair and apoptotic activities of ING1 require the interaction of the C-terminal plant homeodomain (PHD) finger with histone H3 trimethylated at Lys4 (H3K4me3). The ING1 PHD finger recognizes methylated H3K4 but not other histone modifications as revealed by the peptide microarrays. The molecular mechanism of the histone recognition is elucidated based on a 2.1 A-resolution crystal structure of the PHD-H3K4me3 complex. The K4me3 occupies a deep hydrophobic pocket formed by the conserved Y212 and W235 residues that make cation-pi contacts with the trimethylammonium group. Both aromatic residues are essential in the H3K4me3 recognition, as substitution of these residues with Ala disrupts the interaction. Unlike the wild-type ING1, the W235A mutant, overexpressed in the stable clones of melanoma cells or in HT1080 cells, was unable to stimulate DNA repair after UV irradiation or promote DNA-damage-induced apoptosis, indicating that H3K4me3 binding is necessary for these biological functions of ING1. Furthermore, N216S, V218I, and G221V mutations, found in human malignancies, impair the ability of ING1 to associate with H3K4me3 or to induce nucleotide repair and cell death, linking the tumorigenic activity of ING1 with epigenetic regulation. Together, our findings reveal the critical role of the H3K4me3 interaction in mediating cellular responses to genotoxic stresses and offer new insight into the molecular mechanism underlying the tumor suppressive activity of ING1.

Histone H3K4me3 binding is required for the DNA repair and apoptotic activities of ING1 tumor suppressor.,Pena PV, Hom RA, Hung T, Lin H, Kuo AJ, Wong RP, Subach OM, Champagne KS, Zhao R, Verkhusha VV, Li G, Gozani O, Kutateladze TG J Mol Biol. 2008 Jul 4;380(2):303-12. Epub 2008 May 2. PMID:18533182^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Gunduz M, Ouchida M, Fukushima K, Hanafusa H, Etani T, Nishioka S, Nishizaki K, Shimizu K. Genomic structure of the human ING1 gene and tumor-specific mutations detected in head and neck squamous cell carcinomas. Cancer Res. 2000 Jun 15;60(12):3143-6. PMID:10866301
↑ Garkavtsev I, Grigorian IA, Ossovskaya VS, Chernov MV, Chumakov PM, Gudkov AV. The candidate tumour suppressor p33ING1 cooperates with p53 in cell growth control. Nature. 1998 Jan 15;391(6664):295-8. PMID:9440695 doi:10.1038/34675
↑ Pena PV, Hom RA, Hung T, Lin H, Kuo AJ, Wong RP, Subach OM, Champagne KS, Zhao R, Verkhusha VV, Li G, Gozani O, Kutateladze TG. Histone H3K4me3 binding is required for the DNA repair and apoptotic activities of ING1 tumor suppressor. J Mol Biol. 2008 Jul 4;380(2):303-12. Epub 2008 May 2. PMID:18533182 doi:10.1016/j.jmb.2008.04.061

1 Structural highlights
2 Disease
3 Function
4 Evolutionary Conservation
5 Publication Abstract from PubMed
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2qic"

@@ Line 1: / Line 1: @@
 ==Crystal Structure of the ING1 PHD Finger in complex with a Histone H3K4ME3 peptide==
 <StructureSection load='2qic' size='340' side='right' caption='[[2qic]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
@@ Line 6: / Line 7: @@
 <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></td></tr>
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ING1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=2qic FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qic OCA], [http://pdbe.org/2qic PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2qic RCSB], [http://www.ebi.ac.uk/pdbsum/2qic PDBsum]</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=2qic FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qic OCA], [http://pdbe.org/2qic PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2qic RCSB], [http://www.ebi.ac.uk/pdbsum/2qic PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2qic ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 16: / Line 17: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/qi/2qic_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/qi/2qic_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>

2qic

From Proteopedia

Revision as of 11:27, 5 September 2018

Crystal Structure of the ING1 PHD Finger in complex with a Histone H3K4ME3 peptide

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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