2zo2: Difference between revisions
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<StructureSection load='2zo2' size='340' side='right'caption='[[2zo2]], [[Resolution|resolution]] 3.09Å' scene=''> | <StructureSection load='2zo2' size='340' side='right'caption='[[2zo2]], [[Resolution|resolution]] 3.09Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[2zo2]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/ | <table><tr><td colspan='2'>[[2zo2]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ZO2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2ZO2 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]] 3.09Å</td></tr> | ||
<tr id=' | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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=2zo2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2zo2 OCA], [https://pdbe.org/2zo2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2zo2 RCSB], [https://www.ebi.ac.uk/pdbsum/2zo2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2zo2 ProSAT]</span></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=2zo2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2zo2 OCA], [https://pdbe.org/2zo2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2zo2 RCSB], [https://www.ebi.ac.uk/pdbsum/2zo2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2zo2 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[https://www.uniprot.org/uniprot/UHRF1_MOUSE UHRF1_MOUSE] 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:12084726</ref> <ref>PMID:12058012</ref> <ref>PMID:14993289</ref> <ref>PMID:15361834</ref> <ref>PMID:17994007</ref> <ref>PMID:17673620</ref> <ref>PMID:21489993</ref> <ref>PMID:21268065</ref> | |||
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
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</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: | [[Category: Mus musculus]] | ||
[[Category: Cheng | [[Category: Cheng X]] | ||
[[Category: Hashimoto | [[Category: Hashimoto H]] | ||
[[Category: Horton | [[Category: Horton JR]] | ||
Latest revision as of 16:45, 1 November 2023
Mouse NP95 SRA domain non-specific DNA complexMouse NP95 SRA domain non-specific DNA complex
Structural highlights
FunctionUHRF1_MOUSE 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.[1] [2] [3] [4] [5] [6] [7] [8] 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 PubMedMaintenance methylation of hemimethylated CpG dinucleotides at DNA replication forks is the key to faithful mitotic inheritance of genomic methylation patterns. UHRF1 (ubiquitin-like, containing PHD and RING finger domains 1) is required for maintenance methylation by interacting with DNA nucleotide methyltransferase 1 (DNMT1), the maintenance methyltransferase, and with hemimethylated CpG, the substrate for DNMT1 (refs 1 and 2). Here we present the crystal structure of the SET and RING-associated (SRA) domain of mouse UHRF1 in complex with DNA containing a hemimethylated CpG site. The DNA is contacted in both the major and minor grooves by two loops that penetrate into the middle of the DNA helix. The 5-methylcytosine has flipped completely out of the DNA helix and is positioned in a binding pocket with planar stacking contacts, Watson-Crick polar hydrogen bonds and van der Waals interactions specific for 5-methylcytosine. Hence, UHRF1 contains a previously unknown DNA-binding module and is the first example of a non-enzymatic, sequence-specific DNA-binding protein domain to use the base flipping mechanism to interact with DNA. The SRA domain of UHRF1 flips 5-methylcytosine out of the DNA helix.,Hashimoto H, Horton JR, Zhang X, Bostick M, Jacobsen SE, Cheng X Nature. 2008 Oct 9;455(7214):826-9. Epub 2008 Sep 3. PMID:18772888[9] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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