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| | ==Crystal structure of the complex between LubX/LegU2/Lpp2887 U-box 1 and Homo sapiens UBE2D2== | | ==Crystal structure of the complex between LubX/LegU2/Lpp2887 U-box 1 and Homo sapiens UBE2D2== |
| - | <StructureSection load='4wz3' size='340' side='right' caption='[[4wz3]], [[Resolution|resolution]] 2.70Å' scene=''> | + | <StructureSection load='4wz3' size='340' side='right'caption='[[4wz3]], [[Resolution|resolution]] 2.70Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4wz3]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Legpa Legpa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4WZ3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4WZ3 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4wz3]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Legionella_pneumophila_str._Paris Legionella pneumophila str. Paris]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4WZ3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4WZ3 FirstGlance]. <br> |
| - | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</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]] 2.7Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4wz0|4wz0]], [[4wz1|4wz1]], [[4wz2|4wz2]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">UBE2D2, PUBC1, UBC4, UBC5B, UBCH4, UBCH5B ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), lubX, lpp2887 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=297246 LEGPA])</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=4wz3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4wz3 OCA], [https://pdbe.org/4wz3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4wz3 RCSB], [https://www.ebi.ac.uk/pdbsum/4wz3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4wz3 ProSAT]</span></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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4wz3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4wz3 OCA], [http://pdbe.org/4wz3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4wz3 RCSB], [http://www.ebi.ac.uk/pdbsum/4wz3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4wz3 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/UB2D2_HUMAN UB2D2_HUMAN]] Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. In vitro catalyzes 'Lys-48'-linked polyubiquitination. Mediates the selective degradation of short-lived and abnormal proteins. Functions in the E6/E6-AP-induced ubiquitination of p53/TP53. Mediates ubiquitination of PEX5 and autoubiquitination of STUB1 and TRAF6. Involved in the signal-induced conjugation and subsequent degradation of NFKBIA, FBXW2-mediated GCM1 ubiquitination and degradation, MDM2-dependent degradation of p53/TP53 and the activation of MAVS in the mitochondria by DDX58/RIG-I in response to viral infection. Essential for viral activation of IRF3.<ref>PMID:10329681</ref> <ref>PMID:15280377</ref> <ref>PMID:18042044</ref> <ref>PMID:18703417</ref> <ref>PMID:18359941</ref> <ref>PMID:19854139</ref> <ref>PMID:20403326</ref> <ref>PMID:20061386</ref> [[http://www.uniprot.org/uniprot/LUBX_LEGPA LUBX_LEGPA]] Effector proteins function to alter host cell physiology and promote bacterial survival in host tissues. This protein is an E3 ubiquitin ligase that interferes with host's ubiquitination pathway (By similarity). | + | [https://www.uniprot.org/uniprot/UB2D2_HUMAN UB2D2_HUMAN] Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. In vitro catalyzes 'Lys-48'-linked polyubiquitination. Mediates the selective degradation of short-lived and abnormal proteins. Functions in the E6/E6-AP-induced ubiquitination of p53/TP53. Mediates ubiquitination of PEX5 and autoubiquitination of STUB1 and TRAF6. Involved in the signal-induced conjugation and subsequent degradation of NFKBIA, FBXW2-mediated GCM1 ubiquitination and degradation, MDM2-dependent degradation of p53/TP53 and the activation of MAVS in the mitochondria by DDX58/RIG-I in response to viral infection. Essential for viral activation of IRF3.<ref>PMID:10329681</ref> <ref>PMID:15280377</ref> <ref>PMID:18042044</ref> <ref>PMID:18703417</ref> <ref>PMID:18359941</ref> <ref>PMID:19854139</ref> <ref>PMID:20403326</ref> <ref>PMID:20061386</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 4wz3" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 4wz3" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Ubiquitin protein ligase 3D structures|Ubiquitin protein ligase 3D structures]] |
| | + | *[[3D structures of ubiquitin conjugating enzyme|3D structures of ubiquitin conjugating enzyme]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Legpa]] | + | [[Category: Large Structures]] |
| - | [[Category: Ubiquitin--protein ligase]] | + | [[Category: Legionella pneumophila str. Paris]] |
| - | [[Category: Joachimiak, A]]
| + | [[Category: Di Leo R]] |
| - | [[Category: Leo, R Di]] | + | [[Category: Joachimiak A]] |
| - | [[Category: Structural genomic]] | + | [[Category: Nocek B]] |
| - | [[Category: Nocek, B]] | + | [[Category: Quaile AT]] |
| - | [[Category: Quaile, A T]] | + | [[Category: Savchenko A]] |
| - | [[Category: Savchenko, A]] | + | [[Category: Skarina T]] |
| - | [[Category: Skarina, T]] | + | [[Category: Stogios PJ]] |
| - | [[Category: Stogios, P J]] | + | [[Category: Yim V]] |
| - | [[Category: Yim, V]] | + | |
| - | [[Category: Activating enzyme]]
| + | |
| - | [[Category: Alpha/beta protein]]
| + | |
| - | [[Category: Effector]]
| + | |
| - | [[Category: Ligase]]
| + | |
| - | [[Category: Mcsg]]
| + | |
| - | [[Category: Psi-biology]]
| + | |
| Structural highlights
Function
UB2D2_HUMAN Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. In vitro catalyzes 'Lys-48'-linked polyubiquitination. Mediates the selective degradation of short-lived and abnormal proteins. Functions in the E6/E6-AP-induced ubiquitination of p53/TP53. Mediates ubiquitination of PEX5 and autoubiquitination of STUB1 and TRAF6. Involved in the signal-induced conjugation and subsequent degradation of NFKBIA, FBXW2-mediated GCM1 ubiquitination and degradation, MDM2-dependent degradation of p53/TP53 and the activation of MAVS in the mitochondria by DDX58/RIG-I in response to viral infection. Essential for viral activation of IRF3.[1] [2] [3] [4] [5] [6] [7] [8]
Publication Abstract from PubMed
LubX is part of the large arsenal of effectors in Legionella pneumophila that are translocated into the host cytosol during infection. Despite such unique features as the presence of two U-box motifs and its targeting of another effector SidH, the molecular basis of LubX activity remains poorly understood. Here we show that the N terminus of LubX is able to activate an extended number of ubiquitin-conjugating (E2) enzymes including UBE2W, UBEL6, and all tested members of UBE2D and UBE2E families. Crystal structures of LubX alone and in complex with UBE2D2 revealed drastic molecular diversification between the two U-box domains, with only the N-terminal U-box retaining E2 recognition features typical for its eukaryotic counterparts. Extensive mutagenesis followed by functional screening in a yeast model system captured functionally important LubX residues including Arg121, critical for interactions with SidH. Combined, these data provide a new molecular insight into the function of this unique pathogenic factor.
Molecular Characterization of LubX: Functional Divergence of the U-Box Fold by Legionella pneumophila.,Quaile AT, Urbanus ML, Stogios PJ, Nocek B, Skarina T, Ensminger AW, Savchenko A Structure. 2015 Jun 18. pii: S0969-2126(15)00223-3. doi:, 10.1016/j.str.2015.05.020. PMID:26146184[9]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Gonen H, Bercovich B, Orian A, Carrano A, Takizawa C, Yamanaka K, Pagano M, Iwai K, Ciechanover A. Identification of the ubiquitin carrier proteins, E2s, involved in signal-induced conjugation and subsequent degradation of IkappaBalpha. J Biol Chem. 1999 May 21;274(21):14823-30. PMID:10329681
- ↑ Saville MK, Sparks A, Xirodimas DP, Wardrop J, Stevenson LF, Bourdon JC, Woods YL, Lane DP. Regulation of p53 by the ubiquitin-conjugating enzymes UbcH5B/C in vivo. J Biol Chem. 2004 Oct 1;279(40):42169-81. Epub 2004 Jul 26. PMID:15280377 doi:10.1074/jbc.M403362200
- ↑ Windheim M, Peggie M, Cohen P. Two different classes of E2 ubiquitin-conjugating enzymes are required for the mono-ubiquitination of proteins and elongation by polyubiquitin chains with a specific topology. Biochem J. 2008 Feb 1;409(3):723-9. PMID:18042044 doi:10.1042/BJ20071338
- ↑ Chiang MH, Chen LF, Chen H. Ubiquitin-conjugating enzyme UBE2D2 is responsible for FBXW2 (F-box and WD repeat domain containing 2)-mediated human GCM1 (glial cell missing homolog 1) ubiquitination and degradation. Biol Reprod. 2008 Nov;79(5):914-20. doi: 10.1095/biolreprod.108.071407. Epub 2008, Aug 13. PMID:18703417 doi:10.1095/biolreprod.108.071407
- ↑ Grou CP, Carvalho AF, Pinto MP, Wiese S, Piechura H, Meyer HE, Warscheid B, Sa-Miranda C, Azevedo JE. Members of the E2D (UbcH5) family mediate the ubiquitination of the conserved cysteine of Pex5p, the peroxisomal import receptor. J Biol Chem. 2008 May 23;283(21):14190-7. doi: 10.1074/jbc.M800402200. Epub 2008 , Mar 22. PMID:18359941 doi:10.1074/jbc.M800402200
- ↑ Zeng W, Xu M, Liu S, Sun L, Chen ZJ. Key role of Ubc5 and lysine-63 polyubiquitination in viral activation of IRF3. Mol Cell. 2009 Oct 23;36(2):315-25. doi: 10.1016/j.molcel.2009.09.037. PMID:19854139 doi:10.1016/j.molcel.2009.09.037
- ↑ Zeng W, Sun L, Jiang X, Chen X, Hou F, Adhikari A, Xu M, Chen ZJ. Reconstitution of the RIG-I pathway reveals a signaling role of unanchored polyubiquitin chains in innate immunity. Cell. 2010 Apr 16;141(2):315-30. doi: 10.1016/j.cell.2010.03.029. PMID:20403326 doi:10.1016/j.cell.2010.03.029
- ↑ 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
- ↑ Quaile AT, Urbanus ML, Stogios PJ, Nocek B, Skarina T, Ensminger AW, Savchenko A. Molecular Characterization of LubX: Functional Divergence of the U-Box Fold by Legionella pneumophila. Structure. 2015 Jun 18. pii: S0969-2126(15)00223-3. doi:, 10.1016/j.str.2015.05.020. PMID:26146184 doi:http://dx.doi.org/10.1016/j.str.2015.05.020
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