5zi6: Difference between revisions
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The | ==The RING domain structure of MEX-3C== | ||
<StructureSection load='5zi6' size='340' side='right' caption='[[5zi6]], [[Resolution|resolution]] 2.20Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5zi6]] is a 8 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ZI6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ZI6 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> | |||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/RING-type_E3_ubiquitin_transferase RING-type E3 ubiquitin transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.2.27 2.3.2.27] </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=5zi6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5zi6 OCA], [http://pdbe.org/5zi6 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5zi6 RCSB], [http://www.ebi.ac.uk/pdbsum/5zi6 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5zi6 ProSAT]</span></td></tr> | |||
</table> | |||
== Disease == | |||
[[http://www.uniprot.org/uniprot/MEX3C_HUMAN MEX3C_HUMAN]] Genetic variations in MEX3C may be associated with susceptibility to essential hypertension.<ref>PMID:17015768</ref> | |||
== Function == | |||
[[http://www.uniprot.org/uniprot/MEX3C_HUMAN MEX3C_HUMAN]] E3 ubiquitin ligase responsible for the post-transcriptional regulation of common HLA-A allotypes. Binds to the 3' UTR of HLA-A2 mRNA, and regulates its levels by promoting mRNA decay. RNA binding is sufficient to prevent translation, but ubiquitin ligase activity is required for mRNA degradation.<ref>PMID:22863774</ref> <ref>PMID:23446422</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
MEX-3C, a novel RNA binding E3 ubiquitin ligases, contains two N-terminal heterogeneous nuclear ribonucleoprotein K homology (KH) domains and C-terminal Ring finger domain. Recent evidence has suggested that human MEX-3C has a strong bondage with carcinogenesis and the MEX-3C-mediated ubiquitination of RIG-I is essential for the antiviral innate immune response. Moreover, the Ring finger domain of MEX-3C could regulate the degradation of HLA-A2 (an MHC-I allotype) mRNA with a novel mechanism. However, the structural basis for the ubiquitination catalyzed by hMEX-3C Ring finger domain remains evasive. In this study, we solved the crystal structure of dimeric Ring finger domain of hMEX-3C and compared it with the complex structure of MDM2/MDMX-UbcH5b-Ub. Our ubiquitination assay demonstrated that the Ring finger domain of hMEX-3C acts as a ubiquitin E3 ligase in vitro, cooperating with specific E2 to mediate ubiquitination. Then, we identified several key residues in Ring finger domain of hMEX-3C possibly involved in the interaction with E2-Ub conjugate and analyzed the E3 ligase activities of wild type and mutants at key sites. Additionally, zinc chelation experiments indicated that the intact structural stability is essential for the self-ubiquitination activity of the Ring finger domain of hMEX-3C. Taken together, our studies provided new insight into the mechanism of the Ring finger domain of hMEX-3C that may play an important role in eliciting antiviral immune responses and therapeutic interventions. | |||
Structural and functional characterization of hMEX-3C Ring finger domain as an E3 ubiquitin ligase.,Moududee SA, Jiang Y, Gilbert N, Xie G, Xu Z, Wu J, Gong Q, Tang Y, Shi Y Protein Sci. 2018 Sep;27(9):1661-1669. doi: 10.1002/pro.3473. PMID:30095198<ref>PMID:30095198</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 5zi6" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: RING-type E3 ubiquitin transferase]] | |||
[[Category: Moududee, S A]] | |||
[[Category: Tang, Y]] | [[Category: Tang, Y]] | ||
[[Category: | [[Category: E3 liagase]] | ||
[[Category: Ligase]] | |||
[[Category: Mex-3c]] | |||
[[Category: Ring domain]] | |||
[[Category: Ubiquitination]] | |||