3o37

From Proteopedia

(Difference between revisions)

Revision as of 13:07, 4 August 2016

Crystal structure of TRIM24 PHD-Bromo complexed with H3(1-10)K4 peptide

Structural highlights

3o37 is a 8 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	3o34, 3o35, 3o36, 3o33
Gene:	TRIM24, RNF82, TIF1, TIF1A (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[TIF1A_HUMAN] Defects in TRIM24 are a cause of thyroid papillary carcinoma (TPC) [MIM:188550]. TPC is a common tumor of the thyroid that typically arises as an irregular, solid or cystic mass from otherwise normal thyroid tissue. Papillary carcinomas are malignant neoplasm characterized by the formation of numerous, irregular, finger-like projections of fibrous stroma that is covered with a surface layer of neoplastic epithelial cells. Note=A chromosomal aberration involving TRIM24/TIF1 is found in thyroid papillary carcinomas. Translocation t(7;10)(q32;q11) with RET. The translocation generates the TRIM24/RET (PTC6) oncogene.

Function

[TIF1A_HUMAN] Transcriptional coactivator that interacts with numerous nuclear receptors and coactivators and modulates the transcription of target genes. Interacts with chromatin depending on histone H3 modifications, having the highest affinity for histone H3 that is both unmodified at 'Lys-4' (H3K4me0) and acetylated at 'Lys-23' (H3K23ac). Has E3 protein-ubiquitin ligase activity. Promotes ubiquitination and proteasomal degradation of p53/TP53. Plays a role in the regulation of cell proliferation and apoptosis, at least in part via its effects on p53/TP53 levels. Up-regulates ligand-dependent transcription activation by AR, GCR/NR3C1, thyroid hormone receptor (TR) and ESR1. Modulates transcription activation by retinoic acid (RA) receptors, including RARA. Plays a role in regulating retinoic acid-dependent proliferation of hepatocytes (By similarity).^[1] ^[2] ^[3]

Publication Abstract from PubMed

Recognition of modified histone species by distinct structural domains within 'reader' proteins plays a critical role in the regulation of gene expression. Readers that simultaneously recognize histones with multiple marks allow transduction of complex chromatin modification patterns into specific biological outcomes. Here we report that chromatin regulator tripartite motif-containing 24 (TRIM24) functions in humans as a reader of dual histone marks by means of tandem plant homeodomain (PHD) and bromodomain (Bromo) regions. The three-dimensional structure of the PHD-Bromo region of TRIM24 revealed a single functional unit for combinatorial recognition of unmodified H3K4 (that is, histone H3 unmodified at lysine 4, H3K4me0) and acetylated H3K23 (histone H3 acetylated at lysine 23, H3K23ac) within the same histone tail. TRIM24 binds chromatin and oestrogen receptor to activate oestrogen-dependent genes associated with cellular proliferation and tumour development. Aberrant expression of TRIM24 negatively correlates with survival of breast cancer patients. The PHD-Bromo of TRIM24 provides a structural rationale for chromatin activation through a non-canonical histone signature, establishing a new route by which chromatin readers may influence cancer pathogenesis.

TRIM24 links a non-canonical histone signature to breast cancer.,Tsai WW, Wang Z, Yiu TT, Akdemir KC, Xia W, Winter S, Tsai CY, Shi X, Schwarzer D, Plunkett W, Aronow B, Gozani O, Fischle W, Hung MC, Patel DJ, Barton MC Nature. 2010 Dec 16;468(7326):927-32. PMID:21164480^[4]

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

References

↑ Teyssier C, Ou CY, Khetchoumian K, Losson R, Stallcup MR. Transcriptional intermediary factor 1alpha mediates physical interaction and functional synergy between the coactivator-associated arginine methyltransferase 1 and glucocorticoid receptor-interacting protein 1 nuclear receptor coactivators. Mol Endocrinol. 2006 Jun;20(6):1276-86. Epub 2005 Dec 1. PMID:16322096 doi:10.1210/me.2005-0393
↑ Allton K, Jain AK, Herz HM, Tsai WW, Jung SY, Qin J, Bergmann A, Johnson RL, Barton MC. Trim24 targets endogenous p53 for degradation. Proc Natl Acad Sci U S A. 2009 Jul 14;106(28):11612-6. doi:, 10.1073/pnas.0813177106. Epub 2009 Jun 25. PMID:19556538 doi:10.1073/pnas.0813177106
↑ Tsai WW, Wang Z, Yiu TT, Akdemir KC, Xia W, Winter S, Tsai CY, Shi X, Schwarzer D, Plunkett W, Aronow B, Gozani O, Fischle W, Hung MC, Patel DJ, Barton MC. TRIM24 links a non-canonical histone signature to breast cancer. Nature. 2010 Dec 16;468(7326):927-32. PMID:21164480 doi:10.1038/nature09542
↑ Tsai WW, Wang Z, Yiu TT, Akdemir KC, Xia W, Winter S, Tsai CY, Shi X, Schwarzer D, Plunkett W, Aronow B, Gozani O, Fischle W, Hung MC, Patel DJ, Barton MC. TRIM24 links a non-canonical histone signature to breast cancer. Nature. 2010 Dec 16;468(7326):927-32. PMID:21164480 doi:10.1038/nature09542

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3o37"

@@ Line 1: / Line 1: @@
 ==Crystal structure of TRIM24 PHD-Bromo complexed with H3(1-10)K4 peptide==
 <StructureSection load='3o37' size='340' side='right' caption='[[3o37]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3o37]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3O37 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3O37 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3o37]] is a 8 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=3O37 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3O37 FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3o34|3o34]], [[3o35|3o35]], [[3o36|3o36]], [[3o33|3o33]]</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TRIM24, RNF82, TIF1, TIF1A ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TRIM24, RNF82, TIF1, TIF1A ([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=3o37 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3o37 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3o37 RCSB], [http://www.ebi.ac.uk/pdbsum/3o37 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=3o37 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3o37 OCA], [http://pdbe.org/3o37 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3o37 RCSB], [http://www.ebi.ac.uk/pdbsum/3o37 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3o37 ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 20: / Line 21: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 3o37" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Homo sapiens]]
+[[Category: Human]]
 [[Category: Patel, D J]]
 [[Category: Wang, Z]]

3o37

From Proteopedia

Revision as of 13:07, 4 August 2016

Crystal structure of TRIM24 PHD-Bromo complexed with H3(1-10)K4 peptide

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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