3fde

From Proteopedia

(Difference between revisions)

Current revision

Mouse UHRF1 SRA domain bound with hemi-methylated CpG DNA, crystal structure in space group C222(1) at 1.4 A resolution

Structural highlights

3fde is a 6 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.41Å
Ligands:	, , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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.^[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 PubMed

Cytosine methylation in DNA is a major epigenetic signal, and plays a central role in propagating chromatin status during cell division. However the mechanistic links between DNA methylation and histone methylation are poorly understood. A multi-domain protein UHRF1 (ubiquitin-like, containing PHD and RING finger domains 1) is required for DNA CpG maintenance methylation at replication forks, and mouse UHRF1-null cells show enhanced susceptibility to DNA replication arrest and DNA damaging agents. Recent data demonstrated that the SET and RING associated (SRA) domain of UHRF1 binds hemimethylated CpG and flips 5-methylcytosine out of the DNA helix, whereas its tandom tudor domain and PHD domain bind the tail of histone H3 in a highly methylation sensitive manner. We hypothesize that UHRF1 brings the two components (histones and DNA) carrying appropriate markers (on the tails of H3 and hemimethylated CpG sites) ready to be assembled into a nucleosome after replication.

UHRF1, a modular multi-domain protein, regulates replication-coupled crosstalk between DNA methylation and histone modifications.,Hashimoto H, Horton JR, Zhang X, Cheng X Epigenetics. 2009 Jan 10;4(1). PMID:19077538^[9]

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

References

↑ Muto M, Kanari Y, Kubo E, Takabe T, Kurihara T, Fujimori A, Tatsumi K. Targeted disruption of Np95 gene renders murine embryonic stem cells hypersensitive to DNA damaging agents and DNA replication blocks. J Biol Chem. 2002 Sep 13;277(37):34549-55. Epub 2002 Jun 25. PMID:12084726 doi:http://dx.doi.org/10.1074/jbc.M205189200
↑ Bonapace IM, Latella L, Papait R, Nicassio F, Sacco A, Muto M, Crescenzi M, Di Fiore PP. Np95 is regulated by E1A during mitotic reactivation of terminally differentiated cells and is essential for S phase entry. J Cell Biol. 2002 Jun 10;157(6):909-14. Epub 2002 Jun 10. PMID:12058012 doi:http://dx.doi.org/10.1083/jcb.200201025
↑ Citterio E, Papait R, Nicassio F, Vecchi M, Gomiero P, Mantovani R, Di Fiore PP, Bonapace IM. Np95 is a histone-binding protein endowed with ubiquitin ligase activity. Mol Cell Biol. 2004 Mar;24(6):2526-35. PMID:14993289
↑ Unoki M, Nishidate T, Nakamura Y. ICBP90, an E2F-1 target, recruits HDAC1 and binds to methyl-CpG through its SRA domain. Oncogene. 2004 Oct 7;23(46):7601-10. PMID:15361834 doi:10.1038/sj.onc.1208053
↑ Sharif J, Muto M, Takebayashi S, Suetake I, Iwamatsu A, Endo TA, Shinga J, Mizutani-Koseki Y, Toyoda T, Okamura K, Tajima S, Mitsuya K, Okano M, Koseki H. The SRA protein Np95 mediates epigenetic inheritance by recruiting Dnmt1 to methylated DNA. Nature. 2007 Dec 6;450(7171):908-12. Epub 2007 Nov 11. PMID:17994007 doi:http://dx.doi.org/10.1038/nature06397
↑ Bostick M, Kim JK, Esteve PO, Clark A, Pradhan S, Jacobsen SE. UHRF1 plays a role in maintaining DNA methylation in mammalian cells. Science. 2007 Sep 21;317(5845):1760-4. Epub 2007 Aug 2. PMID:17673620 doi:10.1126/science.1147939
↑ Nady N, Lemak A, Walker JR, Avvakumov GV, Kareta MS, Achour M, Xue S, Duan S, Allali-Hassani A, Zuo X, Wang YX, Bronner C, Chedin F, Arrowsmith CH, Dhe-Paganon S. Recognition of multivalent histone states associated with heterochromatin by UHRF1. J Biol Chem. 2011 Apr 13. PMID:21489993 doi:10.1074/jbc.M111.234104
↑ Qin W, Leonhardt H, Spada F. Usp7 and Uhrf1 control ubiquitination and stability of the maintenance DNA methyltransferase Dnmt1. J Cell Biochem. 2011 Feb;112(2):439-44. doi: 10.1002/jcb.22998. PMID:21268065 doi:http://dx.doi.org/10.1002/jcb.22998
↑ Hashimoto H, Horton JR, Zhang X, Cheng X. UHRF1, a modular multi-domain protein, regulates replication-coupled crosstalk between DNA methylation and histone modifications. Epigenetics. 2009 Jan 10;4(1). PMID:19077538

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

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

@@ Line 3: / Line 3: @@
 <StructureSection load='3fde' size='340' side='right'caption='[[3fde]], [[Resolution|resolution]] 1.41&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3fde]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3FDE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3FDE FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3fde]] is a 6 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=3FDE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3FDE FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=UNL:UNKNOWN+LIGAND'>UNL</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.41&#8491;</td></tr>
-<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=5CM:5-METHYL-2-DEOXY-CYTIDINE-5-MONOPHOSPHATE'>5CM</scene></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5CM:5-METHYL-2-DEOXY-CYTIDINE-5-MONOPHOSPHATE'>5CM</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=UNL:UNKNOWN+LIGAND'>UNL</scene></td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2zo0|2zo0]], [[2zo1|2zo1]], [[2zo2|2zo2]], [[3f8i|3f8i]], [[3f8j|3f8j]]</div></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Np95, Uhrf1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</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=3fde FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3fde OCA], [https://pdbe.org/3fde PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3fde RCSB], [https://www.ebi.ac.uk/pdbsum/3fde PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3fde ProSAT]</span></td></tr>
 </table>
 == 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>
+[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 ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 39: / Line 37: @@
 </StructureSection>
 [[Category: Large Structures]]
-[[Category: Lk3 transgenic mice]]
+[[Category: Mus musculus]]
-[[Category: Cheng, X]]
+[[Category: Cheng X]]
-[[Category: Hashimoto, H]]
+[[Category: Hashimoto H]]
-[[Category: Horton, J R]]
+[[Category: Horton JR]]
-[[Category: Zhang, X]]
+[[Category: Zhang X]]
-[[Category: Base flipping]]
-[[Category: Cell cycle]]
-[[Category: Developmental protein]]
-[[Category: Dna cpg methylation]]
-[[Category: Dna damage]]
-[[Category: Dna repair]]
-[[Category: Dna-binding]]
-[[Category: Ligase]]
-[[Category: Metal-binding]]
-[[Category: Nucleus]]
-[[Category: Phosphoprotein]]
-[[Category: Sra domain]]
-[[Category: Transcription]]
-[[Category: Transcription regulation]]
-[[Category: Ubl conjugation]]
-[[Category: Ubl conjugation pathway]]
-[[Category: Zinc]]
-[[Category: Zinc-finger]]

3fde

From Proteopedia

Current revision

Mouse UHRF1 SRA domain bound with hemi-methylated CpG DNA, crystal structure in space group C222(1) at 1.4 A resolution

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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