4pw6

From Proteopedia

(Difference between revisions)

Current revision

structure of UHRF2-SRA in complex with a 5hmC-containing DNA, complex II

Structural highlights

4pw6 is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 3.789Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

UHRF2_HUMAN Associated with various cancers. DNA copy number loss is found in multiple kinds of malignancies originating from the brain, breast, stomach, kidney, hematopoietic tissue and lung.

Function

UHRF2_HUMAN E3 ubiquitin-protein ligase that is an intermolecular hub protein in the cell cycle network. Through cooperative DNA and histone binding, may contribute to a tighter epigenetic control of gene expression in differentiated cells. Ubiquitinates cyclins, CCND1 and CCNE1, in an apparently phosphorylation-independent manner and induces G1 arrest. Also ubiquitinates PCNP leading to its degradation by the proteasome. E3 SUMO-, but not ubiquitin-, protein ligase for ZNF131.^[1] ^[2] ^[3] ^[4] ^[5] ^[6]

Publication Abstract from PubMed

Methylated cytosine of CpG dinucleotides in vertebrates may be oxidized by Tet proteins, a process that can lead to DNA demethylation. The predominant oxidation product, 5-hydroxymethylcytosine (5hmC), has been implicated in embryogenesis, cell differentiation, and human diseases. Recently, the SRA domain of UHRF2 (UHRF2-SRA) has been reported to specifically recognize 5hmC, but how UHRF2 recognizes this modification is unclear. Here we report the structure of UHRF2-SRA in complex with a 5hmC-containing DNA. The structure reveals that the conformation of a phenylalanine allows the formation of an optimal 5hmC binding pocket, and a hydrogen bond between the hydroxyl group of 5hmC and UHRF2-SRA is critical for their preferential binding. Further structural and biochemical analyses unveiled the role of SRA domains as a versatile reader of modified DNA, and the knowledge should facilitate further understanding of the biological function of UHRF2 and the comprehension of DNA hydroxymethylation in general.

Structural Basis for Hydroxymethylcytosine Recognition by the SRA Domain of UHRF2.,Zhou T, Xiong J, Wang M, Yang N, Wong J, Zhu B, Xu RM Mol Cell. 2014 May 7. pii: S1097-2765(14)00313-X. doi:, 10.1016/j.molcel.2014.04.003. PMID:24813944^[7]

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

References

↑ Mori T, Li Y, Hata H, Ono K, Kochi H. NIRF, a novel RING finger protein, is involved in cell-cycle regulation. Biochem Biophys Res Commun. 2002 Aug 23;296(3):530-6. PMID:12176013
↑ Li Y, Mori T, Hata H, Homma Y, Kochi H. NIRF induces G1 arrest and associates with Cdk2. Biochem Biophys Res Commun. 2004 Jun 25;319(2):464-8. PMID:15178429 doi:http://dx.doi.org/10.1016/j.bbrc.2004.04.190
↑ Mori T, Li Y, Hata H, Kochi H. NIRF is a ubiquitin ligase that is capable of ubiquitinating PCNP, a PEST-containing nuclear protein. FEBS Lett. 2004 Jan 16;557(1-3):209-14. PMID:14741369
↑ 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
↑ Mori T, Ikeda DD, Fukushima T, Takenoshita S, Kochi H. NIRF constitutes a nodal point in the cell cycle network and is a candidate tumor suppressor. Cell Cycle. 2011 Oct 1;10(19):3284-99. doi: 10.4161/cc.10.19.17176. Epub 2011 Oct, 1. PMID:21952639 doi:http://dx.doi.org/10.4161/cc.10.19.17176
↑ Oh Y, Chung KC. UHRF2, a ubiquitin E3 ligase, acts as a small ubiquitin-like modifier E3 ligase for zinc finger protein 131. J Biol Chem. 2013 Mar 29;288(13):9102-11. doi: 10.1074/jbc.M112.438234. Epub 2013, Feb 12. PMID:23404503 doi:http://dx.doi.org/10.1074/jbc.M112.438234
↑ Zhou T, Xiong J, Wang M, Yang N, Wong J, Zhu B, Xu RM. Structural Basis for Hydroxymethylcytosine Recognition by the SRA Domain of UHRF2. Mol Cell. 2014 May 7. pii: S1097-2765(14)00313-X. doi:, 10.1016/j.molcel.2014.04.003. PMID:24813944 doi:http://dx.doi.org/10.1016/j.molcel.2014.04.003

1 Structural highlights
2 Disease
3 Function
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/4pw6"

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 4pw6 is ON HOLD  until Paper Publication
+==structure of UHRF2-SRA in complex with a 5hmC-containing DNA, complex II==
+<StructureSection load='4pw6' size='340' side='right'caption='[[4pw6]], [[Resolution|resolution]] 3.79&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[4pw6]] is a 4 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=4PW6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4PW6 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]] 3.789&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5HC:2-DEOXY-5-(HYDROXYMETHYL)CYTIDINE+5-(DIHYDROGEN+PHOSPHATE)'>5HC</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=4pw6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4pw6 OCA], [https://pdbe.org/4pw6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4pw6 RCSB], [https://www.ebi.ac.uk/pdbsum/4pw6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4pw6 ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[https://www.uniprot.org/uniprot/UHRF2_HUMAN UHRF2_HUMAN] Associated with various cancers. DNA copy number loss is found in multiple kinds of malignancies originating from the brain, breast, stomach, kidney, hematopoietic tissue and lung.
+== Function ==
+[https://www.uniprot.org/uniprot/UHRF2_HUMAN UHRF2_HUMAN] E3 ubiquitin-protein ligase that is an intermolecular hub protein in the cell cycle network. Through cooperative DNA and histone binding, may contribute to a tighter epigenetic control of gene expression in differentiated cells. Ubiquitinates cyclins, CCND1 and CCNE1, in an apparently phosphorylation-independent manner and induces G1 arrest. Also ubiquitinates PCNP leading to its degradation by the proteasome. E3 SUMO-, but not ubiquitin-, protein ligase for ZNF131.<ref>PMID:12176013</ref> <ref>PMID:15178429</ref> <ref>PMID:14741369</ref> <ref>PMID:15361834</ref> <ref>PMID:21952639</ref> <ref>PMID:23404503</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Methylated cytosine of CpG dinucleotides in vertebrates may be oxidized by Tet proteins, a process that can lead to DNA demethylation. The predominant oxidation product, 5-hydroxymethylcytosine (5hmC), has been implicated in embryogenesis, cell differentiation, and human diseases. Recently, the SRA domain of UHRF2 (UHRF2-SRA) has been reported to specifically recognize 5hmC, but how UHRF2 recognizes this modification is unclear. Here we report the structure of UHRF2-SRA in complex with a 5hmC-containing DNA. The structure reveals that the conformation of a phenylalanine allows the formation of an optimal 5hmC binding pocket, and a hydrogen bond between the hydroxyl group of 5hmC and UHRF2-SRA is critical for their preferential binding. Further structural and biochemical analyses unveiled the role of SRA domains as a versatile reader of modified DNA, and the knowledge should facilitate further understanding of the biological function of UHRF2 and the comprehension of DNA hydroxymethylation in general.
-Authors: Zhou, T., Xiong, J., Wang, M., Yang, N., Wong, J., Zhu, B., Xu. R.M.
+Structural Basis for Hydroxymethylcytosine Recognition by the SRA Domain of UHRF2.,Zhou T, Xiong J, Wang M, Yang N, Wong J, Zhu B, Xu RM Mol Cell. 2014 May 7. pii: S1097-2765(14)00313-X. doi:, 10.1016/j.molcel.2014.04.003. PMID:24813944<ref>PMID:24813944</ref>
-Description: structure of UHRF2-SRA in complex with a 5hmC-containing DNA, complex II
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 4pw6" 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: Wang M]]
+[[Category: Wong J]]
+[[Category: Xiong J]]
+[[Category: Xu RM]]
+[[Category: Yang N]]
+[[Category: Zhou T]]
+[[Category: Zhu B]]

4pw6

From Proteopedia

Current revision

structure of UHRF2-SRA in complex with a 5hmC-containing DNA, complex II

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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