4gy5

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (14:02, 8 November 2023) (edit) (undo)
 
(8 intermediate revisions not shown.)
Line 1: Line 1:
-
'''Unreleased structure'''
 
-
The entry 4gy5 is ON HOLD
+
==Crystal structure of the tandem tudor domain and plant homeodomain of UHRF1 with Histone H3K9me3==
 +
<StructureSection load='4gy5' size='340' side='right'caption='[[4gy5]], [[Resolution|resolution]] 2.96&Aring;' scene=''>
 +
== Structural highlights ==
 +
<table><tr><td colspan='2'>[[4gy5]] is a 6 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=4GY5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4GY5 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]] 2.956&#8491;</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=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=4gy5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gy5 OCA], [https://pdbe.org/4gy5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4gy5 RCSB], [https://www.ebi.ac.uk/pdbsum/4gy5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4gy5 ProSAT]</span></td></tr>
 +
</table>
 +
== Disease ==
 +
[https://www.uniprot.org/uniprot/UHRF1_HUMAN UHRF1_HUMAN] Note=Defects in UHRF1 may be a cause of cancers. Overexpressed in many different forms of human cancers, including bladder, breast, cervical, colorectal and prostate cancers, as well as pancreatic adenocarcinomas, rhabdomyosarcomas and gliomas. Plays an important role in the correlation of histone modification and gene silencing in cancer progression. Expression is associated with a poor prognosis in patients with various cancers, suggesting that it participates in cancer progression.
 +
== Function ==
 +
[https://www.uniprot.org/uniprot/UHRF1_HUMAN UHRF1_HUMAN] Multidomain protein that acts as a key epigenetic regulator by bridging DNA methylation and chromatin modification. Specifically recognizes and binds hemimethylated DNA at replication forks via its YDG domain and recruits DNMT1 methyltransferase to ensure faithful propagation of the DNA methylation patterns through DNA replication. In addition to its role in maintenance of DNA methylation, also plays a key role in chromatin modification: through its tudor-like regions and PHD-type zinc fingers, specifically recognizes and binds histone H3 trimethylated at 'Lys-9' (H3K9me3) and unmethylated at 'Arg-2' (H3R2me0), respectively, and recruits chromatin proteins. Enriched in pericentric heterochromatin where it recruits different chromatin modifiers required for this chromatin replication. Also localizes to euchromatic regions where it negatively regulates transcription possibly by impacting DNA methylation and histone modifications. Has E3 ubiquitin-protein ligase activity by mediating the ubiquitination of target proteins such as histone H3 and PML. It is still unclear how E3 ubiquitin-protein ligase activity is related to its role in chromatin in vivo. May be involved in DNA repair.<ref>PMID:10646863</ref> <ref>PMID:15009091</ref> <ref>PMID:15361834</ref> <ref>PMID:17673620</ref> <ref>PMID:17967883</ref> <ref>PMID:19056828</ref> <ref>PMID:21745816</ref> <ref>PMID:22945642</ref> <ref>PMID:21777816</ref>
 +
<div style="background-color:#fffaf0;">
 +
== Publication Abstract from PubMed ==
 +
UHRF1 is an important epigenetic regulator connecting DNA methylation and histone methylations. UHRF1 is required for maintenance of DNA methylation through recruiting DNMT1 to DNA replication forks. Recent studies have shown that the plant homeodomain (PHD) of UHRF1 recognizes the N terminus of unmodified histone H3, and the interaction is inhibited by methylation of H3R2, whereas the tandem tudor domain (TTD) of UHRF1 recognizes trimethylated histone H3 lysine 9 (H3K9me3). However, how the two domains of UHRF1 coordinately recognize histone methylations remains elusive. In this report, we identified that PHD largely enhances the interaction between TTD and H3K9me3. We present the crystal structure of UHRF1 containing both TTD and PHD (TTD-PHD) in complex with H3K9m3 peptide at 3.0 A resolution. The structure shows that TTD-PHD binds to the H3K9me3 peptide with 1:1 stoichiometry with the two domains connected by the H3K9me3 peptide and a linker region. The TTD interacts with residues Arg-8 and trimethylated Lys-9, and the PHD interacts with residues Ala-1, Arg-2, and Lys-4 of the H3K9me3 peptide. The biochemical experiments indicate that PHD-mediated recognition of unmodified H3 is independent of the TTD, whereas TTD-mediated recognition of H3K9me3 PHD. Thus, both TTD and PHD are essential for specific recognition of H3K9me3 by UHRF1. Interestingly, the H3K9me3 peptide induces conformational changes of TTD-PHD, which do not affect the autoubiquitination activity or hemimethylated DNA binding affinity of UHRF1 in vitro. Taken together, our studies provide structural insight into the coordinated recognition of H3K9me3 by the TTD and PHD of UHRF1.
-
Authors: Cheng, J., Xu, Y.
+
Structural insight into coordinated recognition of trimethylated histone H3 lysine 9 (H3K9me3) by the plant homeodomain (PHD) and tandem tudor domain (TTD) of UHRF1 (ubiquitin-like, containing PHD and RING finger domains, 1) protein.,Cheng J, Yang Y, Fang J, Xiao J, Zhu T, Chen F, Wang P, Li Z, Yang H, Xu Y J Biol Chem. 2013 Jan 11;288(2):1329-39. doi: 10.1074/jbc.M112.415398. Epub 2012 , Nov 16. PMID:23161542<ref>PMID:23161542</ref>
-
Description: Crystal structure of the tandem tudor doamin and plant homeodomain of UHRF1 with Histone H3K9me3
+
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 +
</div>
 +
<div class="pdbe-citations 4gy5" style="background-color:#fffaf0;"></div>
 +
 
 +
==See Also==
 +
*[[Ubiquitin protein ligase 3D structures|Ubiquitin protein ligase 3D structures]]
 +
== References ==
 +
<references/>
 +
__TOC__
 +
</StructureSection>
 +
[[Category: Homo sapiens]]
 +
[[Category: Large Structures]]
 +
[[Category: Chen F]]
 +
[[Category: Cheng J]]
 +
[[Category: Fang J]]
 +
[[Category: Wang P]]
 +
[[Category: Xiao J]]
 +
[[Category: Xu Y]]
 +
[[Category: Yang Y]]
 +
[[Category: Zhu T]]

Current revision

Crystal structure of the tandem tudor domain and plant homeodomain of UHRF1 with Histone H3K9me3

PDB ID 4gy5

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4gy5"
Personal tools