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| | ==The RING domain structure of MEX-3C== | | ==The RING domain structure of MEX-3C== |
| - | <StructureSection load='5zi6' size='340' side='right' caption='[[5zi6]], [[Resolution|resolution]] 2.20Å' scene=''> | + | <StructureSection load='5zi6' size='340' side='right'caption='[[5zi6]], [[Resolution|resolution]] 2.20Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5zi6]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. 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> | + | <table><tr><td colspan='2'>[[5zi6]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. 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 [https://proteopedia.org/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> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.2Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MEX3C ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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/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'>[https://proteopedia.org/fgij/fg.htm?mol=5zi6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5zi6 OCA], [https://pdbe.org/5zi6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5zi6 RCSB], [https://www.ebi.ac.uk/pdbsum/5zi6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5zi6 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=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> | | </table> |
| | == Disease == | | == 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> | + | [https://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 == | | == 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> | + | [https://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.
| + | |
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| - | 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>
| + | ==See Also== |
| - | | + | *[[Ubiquitin protein ligase 3D structures|Ubiquitin protein ligase 3D structures]] |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 5zi6" style="background-color:#fffaf0;"></div>
| + | |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: RING-type E3 ubiquitin transferase]] | + | [[Category: Large Structures]] |
| - | [[Category: Moududee, S A]] | + | [[Category: Moududee SA]] |
| - | [[Category: Tang, Y]] | + | [[Category: Tang Y]] |
| - | [[Category: E3 liagase]]
| + | |
| - | [[Category: Ligase]]
| + | |
| - | [[Category: Mex-3c]]
| + | |
| - | [[Category: Ring domain]]
| + | |
| - | [[Category: Ubiquitination]]
| + | |
| Structural highlights
Disease
MEX3C_HUMAN Genetic variations in MEX3C may be associated with susceptibility to essential hypertension.[1]
Function
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.[2] [3]
See Also
References
- ↑ Guzman B, Cormand B, Ribases M, Gonzalez-Nunez D, Botey A, Poch E. Implication of chromosome 18 in hypertension by sibling pair and association analyses: putative involvement of the RKHD2 gene. Hypertension. 2006 Nov;48(5):883-91. Epub 2006 Oct 2. PMID:17015768 doi:http://dx.doi.org/10.1161/01.HYP.0000244085.52918.a0
- ↑ Cano F, Bye H, Duncan LM, Buchet-Poyau K, Billaud M, Wills MR, Lehner PJ. The RNA-binding E3 ubiquitin ligase MEX-3C links ubiquitination with MHC-I mRNA degradation. EMBO J. 2012 Aug 29;31(17):3596-606. doi: 10.1038/emboj.2012.218. Epub 2012 Aug, 3. PMID:22863774 doi:http://dx.doi.org/10.1038/emboj.2012.218
- ↑ Burrell RA, McClelland SE, Endesfelder D, Groth P, Weller MC, Shaikh N, Domingo E, Kanu N, Dewhurst SM, Gronroos E, Chew SK, Rowan AJ, Schenk A, Sheffer M, Howell M, Kschischo M, Behrens A, Helleday T, Bartek J, Tomlinson IP, Swanton C. Replication stress links structural and numerical cancer chromosomal instability. Nature. 2013 Feb 28;494(7438):492-496. doi: 10.1038/nature11935. PMID:23446422 doi:http://dx.doi.org/10.1038/nature11935
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