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| | ==NMR structure of the ubiquitin-binding zinc finger (UBZ) domain from human Rad18== | | ==NMR structure of the ubiquitin-binding zinc finger (UBZ) domain from human Rad18== |
| - | <StructureSection load='2mrf' size='340' side='right'caption='[[2mrf]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='2mrf' size='340' side='right'caption='[[2mrf]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2mrf]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2MRF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2MRF FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2mrf]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2MRF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2MRF FirstGlance]. <br> |
| | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">RAD18, RNF73 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=2mrf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2mrf OCA], [https://pdbe.org/2mrf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2mrf RCSB], [https://www.ebi.ac.uk/pdbsum/2mrf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2mrf 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=2mrf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2mrf OCA], [https://pdbe.org/2mrf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2mrf RCSB], [https://www.ebi.ac.uk/pdbsum/2mrf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2mrf ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/RAD18_HUMAN RAD18_HUMAN]] E3 ubiquitin-protein ligase involved in postreplication repair of UV-damaged DNA. Postreplication repair functions in gap-filling of a daughter strand on replication of damaged DNA. Associates to the E2 ubiquitin conjugating enzyme UBE2B to form the UBE2B-RAD18 ubiquitin ligase complex involved in mono-ubiquitination of DNA-associated PCNA on 'Lys-164'. Has ssDNA binding activity.<ref>PMID:17108083</ref> <ref>PMID:21659603</ref>
| + | [https://www.uniprot.org/uniprot/RAD18_HUMAN RAD18_HUMAN] E3 ubiquitin-protein ligase involved in postreplication repair of UV-damaged DNA. Postreplication repair functions in gap-filling of a daughter strand on replication of damaged DNA. Associates to the E2 ubiquitin conjugating enzyme UBE2B to form the UBE2B-RAD18 ubiquitin ligase complex involved in mono-ubiquitination of DNA-associated PCNA on 'Lys-164'. Has ssDNA binding activity.<ref>PMID:17108083</ref> <ref>PMID:21659603</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Bezsonova, I]] | + | [[Category: Bezsonova I]] |
| - | [[Category: Korzhnev, D M]] | + | [[Category: Korzhnev DM]] |
| - | [[Category: Rizzo, A A]] | + | [[Category: Rizzo AA]] |
| - | [[Category: Salerno, P E]] | + | [[Category: Salerno PE]] |
| - | [[Category: Dna repair]]
| + | |
| - | [[Category: Ligase]]
| + | |
| - | [[Category: Translesion synthesis]]
| + | |
| Structural highlights
Function
RAD18_HUMAN E3 ubiquitin-protein ligase involved in postreplication repair of UV-damaged DNA. Postreplication repair functions in gap-filling of a daughter strand on replication of damaged DNA. Associates to the E2 ubiquitin conjugating enzyme UBE2B to form the UBE2B-RAD18 ubiquitin ligase complex involved in mono-ubiquitination of DNA-associated PCNA on 'Lys-164'. Has ssDNA binding activity.[1] [2]
Publication Abstract from PubMed
Ubiquitin-mediated interactions are critical for the cellular DNA damage response (DDR). Therefore, many DDR-related proteins contain ubiquitin-binding domains, including ubiquitin-binding zinc fingers (UBZs). The majority of these UBZ domains belong to the C2H2 (type 3 Poleta-like) or C2HC (type 4 Rad18-like) family. We have used nuclear magnetic resonance (NMR) spectroscopy to characterize the binding to ubiquitin and determine the structure of the type 4 UBZ domain (UBZ4) from human Rad18, which is a key ubiquitin ligase in the DNA damage tolerance pathway responsible for monoubiquitination of the DNA sliding clamp PCNA. The Rad18-UBZ domain binds ubiquitin with micromolar affinity and adopts a beta1-beta2-alpha fold similar to the previously characterized type 3 UBZ domain (UBZ3) from the translesion synthesis DNA polymerase Poleta. However, despite nearly identical structures, a disparity in the location of binding-induced NMR chemical shift perturbations shows that the Rad18-UBZ4 and Poleta-UBZ3 domains bind ubiquitin in distinctly different modes. The Rad18-UBZ4 domain interacts with ubiquitin with the alpha-helix and strand beta1 as shown by the structure of the Rad18-UBZ domain-ubiquitin complex determined in this work, while the Poleta-UBZ3 domain exclusively utilizes the alpha-helix. Our findings suggest the existence of two classes of UBZ domains in DDR-related proteins with similar structures but unique ubiquitin binding properties and provide context for further study to establish the differential roles of these domains in the complex cellular response to DNA damage.
NMR Structure of the Human Rad18 Zinc Finger in Complex with Ubiquitin Defines a Class of UBZ Domains in Proteins Linked to the DNA Damage Response.,Rizzo AA, Salerno PE, Bezsonova I, Korzhnev DM Biochemistry. 2014 Sep 23;53(37):5895-906. doi: 10.1021/bi500823h. Epub 2014 Sep , 15. PMID:25162118[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Unk I, Hajdu I, Fatyol K, Szakal B, Blastyak A, Bermudez V, Hurwitz J, Prakash L, Prakash S, Haracska L. Human SHPRH is a ubiquitin ligase for Mms2-Ubc13-dependent polyubiquitylation of proliferating cell nuclear antigen. Proc Natl Acad Sci U S A. 2006 Nov 28;103(48):18107-12. Epub 2006 Nov 15. PMID:17108083 doi:0608595103
- ↑ Cotta-Ramusino C, McDonald ER 3rd, Hurov K, Sowa ME, Harper JW, Elledge SJ. A DNA damage response screen identifies RHINO, a 9-1-1 and TopBP1 interacting protein required for ATR signaling. Science. 2011 Jun 10;332(6035):1313-7. doi: 10.1126/science.1203430. PMID:21659603 doi:10.1126/science.1203430
- ↑ Rizzo AA, Salerno PE, Bezsonova I, Korzhnev DM. NMR Structure of the Human Rad18 Zinc Finger in Complex with Ubiquitin Defines a Class of UBZ Domains in Proteins Linked to the DNA Damage Response. Biochemistry. 2014 Sep 23;53(37):5895-906. doi: 10.1021/bi500823h. Epub 2014 Sep , 15. PMID:25162118 doi:http://dx.doi.org/10.1021/bi500823h
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