|
|
| Line 3: |
Line 3: |
| | <StructureSection load='6ww4' size='340' side='right'caption='[[6ww4]], [[Resolution|resolution]] 2.25Å' scene=''> | | <StructureSection load='6ww4' size='340' side='right'caption='[[6ww4]], [[Resolution|resolution]] 2.25Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6ww4]] is a 2 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=6WW4 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6WW4 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6ww4]] is a 2 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=6WW4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6WW4 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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]] 2.252Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HERC2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Transferase Transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.2.26 2.3.2.26] </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=6ww4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ww4 OCA], [https://pdbe.org/6ww4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ww4 RCSB], [https://www.ebi.ac.uk/pdbsum/6ww4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ww4 ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6ww4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ww4 OCA], [http://pdbe.org/6ww4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ww4 RCSB], [http://www.ebi.ac.uk/pdbsum/6ww4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ww4 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/HERC2_HUMAN HERC2_HUMAN] E3 ubiquitin-protein ligase that regulates ubiquitin-dependent retention of repair proteins on damaged chromosomes. Recruited to sites of DNA damage in response to ionizing radiation (IR) and facilitates the assembly of UBE2N and RNF8 promoting DNA damage-induced formation of 'Lys-63'-linked ubiquitin chains. Acts as a mediator of binding specificity between UBE2N and RNF8. Involved in the maintenance of RNF168 levels. E3 ubiquitin-protein ligase that promotes the ubiquitination and proteasomal degradation of XPA which influences the circadian oscillation of DNA excision repair activity.<ref>PMID:20023648</ref> <ref>PMID:20304803</ref> <ref>PMID:22508508</ref> [https://www.uniprot.org/uniprot/H31_HUMAN H31_HUMAN] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 22: |
Line 23: |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Transferase]]
| + | [[Category: Kutateladze TG]] |
| - | [[Category: Kutateladze, T G]] | + | [[Category: Liu J]] |
| - | [[Category: Liu, J]] | + | [[Category: Vann KR]] |
| - | [[Category: Vann, K R]] | + | |
| - | [[Category: Gene regulation]]
| + | |
| - | [[Category: Herc2]]
| + | |
| - | [[Category: Histone reader]]
| + | |
| - | [[Category: Zinc finger protein]]
| + | |
| - | [[Category: Zz domain]]
| + | |
| Structural highlights
Function
HERC2_HUMAN E3 ubiquitin-protein ligase that regulates ubiquitin-dependent retention of repair proteins on damaged chromosomes. Recruited to sites of DNA damage in response to ionizing radiation (IR) and facilitates the assembly of UBE2N and RNF8 promoting DNA damage-induced formation of 'Lys-63'-linked ubiquitin chains. Acts as a mediator of binding specificity between UBE2N and RNF8. Involved in the maintenance of RNF168 levels. E3 ubiquitin-protein ligase that promotes the ubiquitination and proteasomal degradation of XPA which influences the circadian oscillation of DNA excision repair activity.[1] [2] [3] H31_HUMAN
Publication Abstract from PubMed
Human ubiquitin ligase HERC2, a component of the DNA repair machinery, has been linked to neurological diseases and cancer. Here, we show that the ZZ domain of HERC2 (HERC2ZZ) binds to histone H3 tail and tolerates posttranslational modifications commonly present in H3. The crystal structure of the HERC2ZZ:H3 complex provides the molecular basis for this interaction and highlights a critical role of the negatively charged site of HERC2ZZ in capturing of A1 of H3. NMR, mutagenesis, and fluorescence data reveal that HERC2ZZ binds to H3 and the N-terminal tail of SUMO1, a previously reported ligand of HERC2ZZ, with comparable affinities. Like H3, the N-terminal tail of SUMO1 occupies the same negatively charged site of HERC2ZZ in the crystal structure of the complex, although in contrast to H3 it adopts an alpha-helical conformation. Our data suggest that HERC2ZZ may play a role in mediating the association of HERC2 with chromatin.
Structural Insight into Binding of the ZZ Domain of HERC2 to Histone H3 and SUMO1.,Liu J, Xue Z, Zhang Y, Vann KR, Shi X, Kutateladze TG Structure. 2020 Jul 23. pii: S0969-2126(20)30236-7. doi:, 10.1016/j.str.2020.07.003. PMID:32726574[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Bekker-Jensen S, Danielsen JR, Fugger K, Gromova I, Nerstedt A, Bartek J, Lukas J, Mailand N. HERC2 coordinates ubiquitin-dependent assembly of DNA repair factors on damaged chromosomes. Nat Cell Biol. 2010 Jan;12(1):80-6; sup pp 1-12. Epub 2009 Dec 20. PMID:20023648 doi:ncb2008
- ↑ Kang TH, Lindsey-Boltz LA, Reardon JT, Sancar A. Circadian control of XPA and excision repair of cisplatin-DNA damage by cryptochrome and HERC2 ubiquitin ligase. Proc Natl Acad Sci U S A. 2010 Mar 16;107(11):4890-5. doi:, 10.1073/pnas.0915085107. PMID:20304803 doi:10.1073/pnas.0915085107
- ↑ Danielsen JR, Povlsen LK, Villumsen BH, Streicher W, Nilsson J, Wikstrom M, Bekker-Jensen S, Mailand N. DNA damage-inducible SUMOylation of HERC2 promotes RNF8 binding via a novel SUMO-binding Zinc finger. J Cell Biol. 2012 Apr 16;197(2):179-87. doi: 10.1083/jcb.201106152. PMID:22508508 doi:10.1083/jcb.201106152
- ↑ Liu J, Xue Z, Zhang Y, Vann KR, Shi X, Kutateladze TG. Structural Insight into Binding of the ZZ Domain of HERC2 to Histone H3 and SUMO1. Structure. 2020 Jul 23. pii: S0969-2126(20)30236-7. doi:, 10.1016/j.str.2020.07.003. PMID:32726574 doi:http://dx.doi.org/10.1016/j.str.2020.07.003
|
