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| | ==Structual basis for the recognition of Ubc13 by the Shigella flexneri effector OspI== | | ==Structual basis for the recognition of Ubc13 by the Shigella flexneri effector OspI== |
| - | <StructureSection load='3w31' size='340' side='right' caption='[[3w31]], [[Resolution|resolution]] 2.96Å' scene=''> | + | <StructureSection load='3w31' size='340' side='right'caption='[[3w31]], [[Resolution|resolution]] 2.96Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3w31]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/"shigella_paradysenteriae"_weldin_1927 "shigella paradysenteriae" weldin 1927] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3W31 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3W31 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3w31]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/"shigella_paradysenteriae"_weldin_1927 "shigella paradysenteriae" weldin 1927] and [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3W31 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3W31 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=IOD:IODIDE+ION'>IOD</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=IOD:IODIDE+ION'>IOD</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3w30|3w30]]</td></tr> | + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3w30|3w30]]</div></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ORF169b, CP0209 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=623 "Shigella paradysenteriae" Weldin 1927]), UBE2N, BLU ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ORF169b, CP0209 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=623 "Shigella paradysenteriae" Weldin 1927]), UBE2N, BLU ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Ubiquitin--protein_ligase Ubiquitin--protein ligase], with EC number [https://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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3w31 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3w31 OCA], [http://pdbe.org/3w31 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3w31 RCSB], [http://www.ebi.ac.uk/pdbsum/3w31 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3w31 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=3w31 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3w31 OCA], [https://pdbe.org/3w31 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3w31 RCSB], [https://www.ebi.ac.uk/pdbsum/3w31 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3w31 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/UBE2N_HUMAN UBE2N_HUMAN]] The UBE2V1-UBE2N and UBE2V2-UBE2N heterodimers catalyze the synthesis of non-canonical 'Lys-63'-linked polyubiquitin chains. This type of polyubiquitination does not lead to protein degradation by the proteasome. Mediates transcriptional activation of target genes. Plays a role in the control of progress through the cell cycle and differentiation. Plays a role in the error-free DNA repair pathway and contributes to the survival of cells after DNA damage. Acts together with the E3 ligases, HLTF and SHPRH, in the 'Lys-63'-linked poly-ubiquitination of PCNA upon genotoxic stress, which is required for DNA repair. Appears to act together with E3 ligase RNF5 in the 'Lys-63'-linked polyubiquitination of JKAMP thereby regulating JKAMP function by decreasing its association with components of the proteasome and ERAD. Promotes TRIM5 capsid-specific restriction activity and the UBE2V1-UBE2N heterodimer acts in concert with TRIM5 to generate 'Lys-63'-linked polyubiquitin chains which activate the MAP3K7/TAK1 complex which in turn results in the induction and expression of NF-kappa-B and MAPK-responsive inflammatory genes (By similarity).<ref>PMID:10089880</ref> <ref>PMID:14562038</ref> <ref>PMID:19269966</ref> <ref>PMID:20061386</ref> <ref>PMID:21512573</ref> | + | [[https://www.uniprot.org/uniprot/UBE2N_HUMAN UBE2N_HUMAN]] The UBE2V1-UBE2N and UBE2V2-UBE2N heterodimers catalyze the synthesis of non-canonical 'Lys-63'-linked polyubiquitin chains. This type of polyubiquitination does not lead to protein degradation by the proteasome. Mediates transcriptional activation of target genes. Plays a role in the control of progress through the cell cycle and differentiation. Plays a role in the error-free DNA repair pathway and contributes to the survival of cells after DNA damage. Acts together with the E3 ligases, HLTF and SHPRH, in the 'Lys-63'-linked poly-ubiquitination of PCNA upon genotoxic stress, which is required for DNA repair. Appears to act together with E3 ligase RNF5 in the 'Lys-63'-linked polyubiquitination of JKAMP thereby regulating JKAMP function by decreasing its association with components of the proteasome and ERAD. Promotes TRIM5 capsid-specific restriction activity and the UBE2V1-UBE2N heterodimer acts in concert with TRIM5 to generate 'Lys-63'-linked polyubiquitin chains which activate the MAP3K7/TAK1 complex which in turn results in the induction and expression of NF-kappa-B and MAPK-responsive inflammatory genes (By similarity).<ref>PMID:10089880</ref> <ref>PMID:14562038</ref> <ref>PMID:19269966</ref> <ref>PMID:20061386</ref> <ref>PMID:21512573</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | ==See Also== | | ==See Also== |
| - | *[[Ubiquitin conjugating enzyme|Ubiquitin conjugating enzyme]] | + | *[[3D structures of ubiquitin conjugating enzyme|3D structures of ubiquitin conjugating enzyme]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | [[Category: Shigella paradysenteriae weldin 1927]] | | [[Category: Shigella paradysenteriae weldin 1927]] |
| | [[Category: Human]] | | [[Category: Human]] |
| | + | [[Category: Large Structures]] |
| | [[Category: Ubiquitin--protein ligase]] | | [[Category: Ubiquitin--protein ligase]] |
| | [[Category: Kim, M]] | | [[Category: Kim, M]] |
| Structural highlights
Function
[UBE2N_HUMAN] The UBE2V1-UBE2N and UBE2V2-UBE2N heterodimers catalyze the synthesis of non-canonical 'Lys-63'-linked polyubiquitin chains. This type of polyubiquitination does not lead to protein degradation by the proteasome. Mediates transcriptional activation of target genes. Plays a role in the control of progress through the cell cycle and differentiation. Plays a role in the error-free DNA repair pathway and contributes to the survival of cells after DNA damage. Acts together with the E3 ligases, HLTF and SHPRH, in the 'Lys-63'-linked poly-ubiquitination of PCNA upon genotoxic stress, which is required for DNA repair. Appears to act together with E3 ligase RNF5 in the 'Lys-63'-linked polyubiquitination of JKAMP thereby regulating JKAMP function by decreasing its association with components of the proteasome and ERAD. Promotes TRIM5 capsid-specific restriction activity and the UBE2V1-UBE2N heterodimer acts in concert with TRIM5 to generate 'Lys-63'-linked polyubiquitin chains which activate the MAP3K7/TAK1 complex which in turn results in the induction and expression of NF-kappa-B and MAPK-responsive inflammatory genes (By similarity).[1] [2] [3] [4] [5]
Publication Abstract from PubMed
Ubc13 is a ubiquitin-conjugating enzyme that plays a key role in the nuclear factor-kappaB signal transduction pathway in human diseases. The Shigella flexneri effector OspI affects inflammatory responses by catalyzing the deamidation of a specific glutamine residue at position 100 in Ubc13 during infection. This modification prevents the activation of the TNF (tumor necrosis factor) receptor-associated factor 6, leading to modulation of the diacylglycerol-CBM (CARD-Bcl10-Malt1) complex-TNF receptor-associated factor 6-nuclear factor-kappaB signaling pathway. To elucidate the structural basis of OspI function, we determined the crystal structures of the catalytically inert OspI C62A mutant and its complex with Ubc13 at resolutions of 3.0 and 2.96A, respectively. The structure of the OspI-Ubc13 complex revealed that the interacting surfaces between OspI and Ubc13 are a hydrophobic surface and a complementary charged surface. Furthermore, we predict that the complementary charged surface of OspI plays a key role in substrate specificity determination.
Structural Basis for the Recognition of Ubc13 by the Shigella flexneri Effector OspI.,Nishide A, Kim M, Takagi K, Himeno A, Sanada T, Sasakawa C, Mizushima T J Mol Biol. 2013 Aug 9;425(15):2623-31. doi: 10.1016/j.jmb.2013.02.037. Epub 2013, Mar 27. PMID:23542009[6]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Hofmann RM, Pickart CM. Noncanonical MMS2-encoded ubiquitin-conjugating enzyme functions in assembly of novel polyubiquitin chains for DNA repair. Cell. 1999 Mar 5;96(5):645-53. PMID:10089880
- ↑ Bothos J, Summers MK, Venere M, Scolnick DM, Halazonetis TD. The Chfr mitotic checkpoint protein functions with Ubc13-Mms2 to form Lys63-linked polyubiquitin chains. Oncogene. 2003 Oct 16;22(46):7101-7. PMID:14562038 doi:10.1038/sj.onc.1206831
- ↑ Tcherpakov M, Delaunay A, Toth J, Kadoya T, Petroski MD, Ronai ZA. Regulation of endoplasmic reticulum-associated degradation by RNF5-dependent ubiquitination of JNK-associated membrane protein (JAMP). J Biol Chem. 2009 May 1;284(18):12099-109. doi: 10.1074/jbc.M808222200. Epub 2009, Mar 6. PMID:19269966 doi:10.1074/jbc.M808222200
- ↑ David Y, Ziv T, Admon A, Navon A. The E2 ubiquitin conjugating enzymes direct polyubiquitination to preferred lysines. J Biol Chem. 2010 Jan 8. PMID:20061386 doi:M109.089003
- ↑ Pertel T, Hausmann S, Morger D, Zuger S, Guerra J, Lascano J, Reinhard C, Santoni FA, Uchil PD, Chatel L, Bisiaux A, Albert ML, Strambio-De-Castillia C, Mothes W, Pizzato M, Grutter MG, Luban J. TRIM5 is an innate immune sensor for the retrovirus capsid lattice. Nature. 2011 Apr 21;472(7343):361-5. doi: 10.1038/nature09976. PMID:21512573 doi:10.1038/nature09976
- ↑ Nishide A, Kim M, Takagi K, Himeno A, Sanada T, Sasakawa C, Mizushima T. Structural Basis for the Recognition of Ubc13 by the Shigella flexneri Effector OspI. J Mol Biol. 2013 Aug 9;425(15):2623-31. doi: 10.1016/j.jmb.2013.02.037. Epub 2013, Mar 27. PMID:23542009 doi:10.1016/j.jmb.2013.02.037
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