View source for 4wz3


==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]] 2.70&Aring;' scene=''>
== Structural highlights ==
<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='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.7&#8491;</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='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>
</table>
== Function ==
[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;">
== 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<ref>PMID:26146184</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</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/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Legionella pneumophila str. Paris]]
[[Category: Di Leo R]]
[[Category: Joachimiak A]]
[[Category: Nocek B]]
[[Category: Quaile AT]]
[[Category: Savchenko A]]
[[Category: Skarina T]]
[[Category: Stogios PJ]]
[[Category: Yim V]]