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| | ==Rnf4 - ubch5a - ubiquitin heterotrimeric complex== | | ==Rnf4 - ubch5a - ubiquitin heterotrimeric complex== |
| - | <StructureSection load='4ap4' size='340' side='right' caption='[[4ap4]], [[Resolution|resolution]] 2.21Å' scene=''> | + | <StructureSection load='4ap4' size='340' side='right'caption='[[4ap4]], [[Resolution|resolution]] 2.21Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4ap4]] is a 5 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4AP4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4AP4 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4ap4]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4AP4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4AP4 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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]] 2.21Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2c4p|2c4p]], [[2yho|2yho]]</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='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Ubiquitin--protein_ligase Ubiquitin--protein ligase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.3.2.19 6.3.2.19] </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=4ap4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ap4 OCA], [https://pdbe.org/4ap4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ap4 RCSB], [https://www.ebi.ac.uk/pdbsum/4ap4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ap4 ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ap4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ap4 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ap4 RCSB], [http://www.ebi.ac.uk/pdbsum/4ap4 PDBsum]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/RNF4_RAT RNF4_RAT] E3 ubiquitin-protein ligase which binds polysumoylated chains covalently attached to proteins and mediates 'Lys-6'-, 'Lys-11'-, 'Lys-48'- and 'Lys-63'-linked polyubiquitination of those substrates and their subsequent targeting to the proteasome for degradation. Regulates the degradation of several proteins including PML and the transcriptional activator PEA3. Involved in chromosome alignment and spindle assembly, it regulates the kinetochore CENPH-CENPI-CENPK complex by targeting polysumoylated CENPI to proteasomal degradation. Regulates the cellular responses to hypoxia and heat shock through degradation of respectively EPAS1 and PARP1. Alternatively, it may also bind DNA/nucleosomes and have a more direct role in the regulation of transcription for instance enhancing basal transcription and steroid receptor-mediated transcriptional activation.<ref>PMID:9710597</ref> <ref>PMID:11319220</ref> <ref>PMID:14987998</ref> <ref>PMID:15707587</ref> <ref>PMID:18408734</ref> <ref>PMID:20943951</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | </div> | | </div> |
| | + | <div class="pdbe-citations 4ap4" style="background-color:#fffaf0;"></div> |
| | | | |
| | ==See Also== | | ==See Also== |
| - | *[[Ubiquitin conjugating enzyme|Ubiquitin conjugating enzyme]] | + | *[[Ubiquitin protein ligase 3D structures|Ubiquitin protein ligase 3D structures]] |
| - | *[[Ubiquitin protein ligase|Ubiquitin protein ligase]] | + | *[[3D structures of ubiquitin conjugating enzyme|3D structures of ubiquitin conjugating enzyme]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| | + | [[Category: Large Structures]] |
| | [[Category: Rattus norvegicus]] | | [[Category: Rattus norvegicus]] |
| - | [[Category: Ubiquitin--protein ligase]]
| + | [[Category: Hay RT]] |
| - | [[Category: Hay, R T]] | + | [[Category: Jaffray E]] |
| - | [[Category: Jaffray, E]] | + | [[Category: Naismith JH]] |
| - | [[Category: Naismith, J H]] | + | [[Category: Plechanovova A]] |
| - | [[Category: Plechanovova, A]] | + | [[Category: Tatham MH]] |
| - | [[Category: Tatham, M H]] | + | |
| - | [[Category: Chimera]]
| + | |
| - | [[Category: Ligase-signalling protein complex]]
| + | |
| Structural highlights
Function
RNF4_RAT E3 ubiquitin-protein ligase which binds polysumoylated chains covalently attached to proteins and mediates 'Lys-6'-, 'Lys-11'-, 'Lys-48'- and 'Lys-63'-linked polyubiquitination of those substrates and their subsequent targeting to the proteasome for degradation. Regulates the degradation of several proteins including PML and the transcriptional activator PEA3. Involved in chromosome alignment and spindle assembly, it regulates the kinetochore CENPH-CENPI-CENPK complex by targeting polysumoylated CENPI to proteasomal degradation. Regulates the cellular responses to hypoxia and heat shock through degradation of respectively EPAS1 and PARP1. Alternatively, it may also bind DNA/nucleosomes and have a more direct role in the regulation of transcription for instance enhancing basal transcription and steroid receptor-mediated transcriptional activation.[1] [2] [3] [4] [5] [6]
Publication Abstract from PubMed
Ubiquitin modification is mediated by a large family of specificity determining ubiquitin E3 ligases. To facilitate ubiquitin transfer, RING E3 ligases bind both substrate and a ubiquitin E2 conjugating enzyme linked to ubiquitin via a thioester bond, but the mechanism of transfer has remained elusive. Here we report the crystal structure of the dimeric RING domain of rat RNF4 in complex with E2 (UbcH5A) linked by an isopeptide bond to ubiquitin. While the E2 contacts a single protomer of the RING, ubiquitin is folded back onto the E2 by contacts from both RING protomers. The carboxy-terminal tail of ubiquitin is locked into an active site groove on the E2 by an intricate network of interactions, resulting in changes at the E2 active site. This arrangement is primed for catalysis as it can deprotonate the incoming substrate lysine residue and stabilize the consequent tetrahedral transition-state intermediate.
Structure of a RING E3 ligase and ubiquitin-loaded E2 primed for catalysis.,Plechanovova A, Jaffray EG, Tatham MH, Naismith JH, Hay RT Nature. 2012 Sep 6;489(7414):115-20. PMID:22842904[7]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Moilanen AM, Poukka H, Karvonen U, Hakli M, Janne OA, Palvimo JJ. Identification of a novel RING finger protein as a coregulator in steroid receptor-mediated gene transcription. Mol Cell Biol. 1998 Sep;18(9):5128-39. PMID:9710597
- ↑ Hakli M, Karvonen U, Janne OA, Palvimo JJ. The RING finger protein SNURF is a bifunctional protein possessing DNA binding activity. J Biol Chem. 2001 Jun 29;276(26):23653-60. Epub 2001 Apr 23. PMID:11319220 doi:10.1074/jbc.M009891200
- ↑ Hakli M, Lorick KL, Weissman AM, Janne OA, Palvimo JJ. Transcriptional coregulator SNURF (RNF4) possesses ubiquitin E3 ligase activity. FEBS Lett. 2004 Feb 27;560(1-3):56-62. PMID:14987998 doi:10.1016/S0014-5793(04)00070-5
- ↑ Hakli M, Karvonen U, Janne OA, Palvimo JJ. SUMO-1 promotes association of SNURF (RNF4) with PML nuclear bodies. Exp Cell Res. 2005 Mar 10;304(1):224-33. Epub 2004 Nov 23. PMID:15707587 doi:10.1016/j.yexcr.2004.10.029
- ↑ Tatham MH, Geoffroy MC, Shen L, Plechanovova A, Hattersley N, Jaffray EG, Palvimo JJ, Hay RT. RNF4 is a poly-SUMO-specific E3 ubiquitin ligase required for arsenic-induced PML degradation. Nat Cell Biol. 2008 May;10(5):538-46. doi: 10.1038/ncb1716. Epub 2008 Apr 13. PMID:18408734 doi:10.1038/ncb1716
- ↑ Geoffroy MC, Jaffray EG, Walker KJ, Hay RT. Arsenic-induced SUMO-dependent recruitment of RNF4 into PML nuclear bodies. Mol Biol Cell. 2010 Dec;21(23):4227-39. doi: 10.1091/mbc.E10-05-0449. Epub 2010, Oct 13. PMID:20943951 doi:10.1091/mbc.E10-05-0449
- ↑ Plechanovova A, Jaffray EG, Tatham MH, Naismith JH, Hay RT. Structure of a RING E3 ligase and ubiquitin-loaded E2 primed for catalysis. Nature. 2012 Sep 6;489(7414):115-20. PMID:22842904 doi:http://dx.doi.org/10.1038/nature11376
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